IP Library › Granted Patent US 12,263,221

Granted Patent B2

US 12,263,221 · App. 18/347,487 · Granted Apr 1, 2025

Chimeric antigen receptor comprising BCMA nanobody linked to a chimeric intracellular signaling domain

Inventors: William A. Comrie (Silver Spring, MD); Wenshan Hao (Parsippany, NJ)

A61K39/464417 A61K39/4611 A61K39/4631 A61P35/00 C07K14/7051 C07K14/70521 C07K16/2878 C12N15/62 A61K2239/13 A61K2239/22 A61K2239/48 C07K2317/569 C07K2319/33

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Quick Facts

Patent No.: US 12,263,221
App. No.: 18/347,487
Granted: Apr 1, 2025
Kind: B2

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Abstract

The present application relates to functionally improved third generation BCMA-CARs comprising modified intracellular co-stimulatory domains, which can be used in adoptive cell therapy, e.g., in treatment of diseases and disorders such as cancer.

Claims (14)

1. A chimeric antigen receptor that binds B cell maturation antigen (BCMA-CAR), comprising:

(a) an extracellular domain comprising the amino acid sequence of SEQ ID NO: 8;

(b) a transmembrane domain; and

(c) a chimeric intracellular domain comprising a first, a second and at least a third signal transduction domain, wherein

the first signal transduction domain consists of an ICOS intracellular domain as set forth in SEQ ID NO: 2,

the second signal transduction domain consists of a truncated CD137 (4-1BB) intracellular domain as set forth in SEQ ID NO: 3, and

the at least third signal transduction domain consists of a truncated CD3ζ domain as set forth in SEQ ID NO: 4,

wherein the BCMA-CAR comprises the amino acid sequence as set forth in SEQ ID NO: 5.

2. An isolated nucleic acid encoding the BCMA-CAR of claim 1 , or a vector comprising a nucleic acid encoding the BCMA-CAR of claim 1 .

3. An isolated T cell comprising the nucleic acid or vector of claim 2 .

4. The isolated T cell of claim 3 , wherein the cell is: a) an allogeneic T cell; or b) an autologous T cell.

5. The isolated T cell of claim 3 , wherein the T cell is a naive T cell, an early memory T cell, a stem cell-like T cell, a stem memory T cell (TSCM), a central memory T cell (TCM), or a regulatory T cell (Treg).

6. The isolated T cell of claim 3 , wherein the T cell co-expresses the BCMA-CAR with at least one endogenous co-stimulatory molecule selected from CD28, CD2, OX-40, ICOS, CD28, CD3, CD4, CD8, CD40L, and a combination thereof.

7. A composition comprising the isolated T-cell of claim 3 .

Assignments (1)

ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Sep 26, 2023

From: COMRIE, WILLIAM A.; HAO, WENSHAN

To: NEOMICS PHARMACEUTICALS LLC

Reel/Frame 065028/0675 →

Continuity (2)

Provisional Application 63358399 · Jul 5, 2022

Related Publication 20240009309A1 · Jan 11, 2024

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GenBank NCBI Reference Sequence: NP_001036106.2, “T-cell-specific surface glycoprotein CD28 precursor [Macaca mulatta],” Jun. 25, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_001070976.1, “tumor necrosis factor receptor superfamily member 9 isoform 2 precursor [Mus musculus],” Apr. 17, 2022, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_001070977.1, “tumor necrosis factor receptor superfamily member 9 isoform 1 precursor [Mus musculus],” Apr. 17, 2022, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_001162597.1, “transmembrane and immunoglobulin domain-containing protein 2 isoform 2 precursor [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_001230006.1, “T-cell-specific surface glycoprotein CD28 isoform 2 precursor [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_001230007.1, “T-cell-specific surface glycoprotein CD28 isoform 3 precursor [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_001253918.1, “inducible T-cell costimulator precursor [Macaca mulatta],” Feb. 21, 2022, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_001274262.1, “T-cell-specific surface glycoprotein CD28 precursor [Macaca fascicularis],” Jun. 30, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_001284491.1, “tumor necrosis factor ligand superfamily member 4 isoform 2 [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_001295161.1, “transmembrane and immunoglobulin domain-containing protein 2 isoform 3 [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_001552.1, “interleukin-activated receptor, homolog of mouse Ly63 [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_003317.1, “tumor necrosis factor ligand superfamily member 4 isoform 1 [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_003318.1, “tumor necrosis factor receptor superfamily member 4 precursor [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_006130.1, “T-cell-specific surface glycoprotein CD28 isoform 1 precursor [ [cited by applicant]

GenBank NCBI Reference Sequence: NP_031668.3, “T-cell-specific surface glycoprotein CD28 precursor [Mus musculus],” Jul. 19, 2022, 4 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_033430.1, “tumor necrosis factor ligand superfamily member 9 [Mus musculus],” May 8, 2022, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_033478.1, “tumor necrosis factor ligand superfamily member 4 [Mus musculus],” Mar. 6, 2022, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_035742.1, “tumor necrosis factor receptor superfamily member 9 isoform 1 precursor [Mus musculus],” Apr. 17, 2022, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_035789.1, “tumor necrosis factor receptor superfamily member 4 precursor [Mus musculus],” Jul. 3, 2022, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_036224.1, “inducible T-cell costimulator precursor [ [cited by applicant]

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GenBank NCBI Reference Sequence: NP_037253.2, “T-cell-specific surface glycoprotein CD28 precursor [Rattus norvegicus],” Jun. 11, 2022, 4 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_059508.2, “inducible T-cell costimulator precursor [Mus musculus],” May 15, 2022, 4 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_072132.1, “inducible T-cell costimulator precursor [Rattus norvegicus],” Jan. 12, 2022, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: NP_852049.1, “tumor necrosis factor ligand superfamily member 9 [Rattus norvegicus],” Feb. 5, 2021, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_001090870.1, “tumor necrosis factor receptor superfamily member 4 [Macaca mulatta],” Apr. 26, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_003890998.2, “tumor necrosis factor receptor superfamily member 4 isoform X1 [Papio anubis],” Nov. 20, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_003907887.1, “inducible T-cell costimulator isoform X2 [Papio anubis],” Nov. 20, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_003925677.1, “inducible T-cell costimulator isoform X1 [Saimiri boliviensis boliviensis],” Feb. 12, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_003939714.1, “Predicted: tumor necrosis factor receptor superfamily member 4 isoform X2 [Saimiri boliviensis boliviensis],” Nov. 24, 2014, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_004851403.1, “T-cell-specific surface glycoprotein CD28 [Heterocephalus glaber],” May 23, 2017, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_005545179.1, “tumor necrosis factor receptor superfamily member 4 isoform X2 [Macaca fascicularis],” Dec. 8, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_005574075.1, “Predicted: inducible T- cell costimulator [Macaca fascicularis],” Jan. 25, 2016, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006239534.1, “tumor necrosis factor receptor superfamily member 9 isoform X1 [Rattus norvegicus],” Jan. 21, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006245099.1, “inducible T-cell costimulator isoform X1 [Rattus norvegicus],” Jan. 21, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006245100.1, “inducible T-cell costimulator isoform X2 [Rattus norvegicus],” Jan. 21, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006256322.1, “Icos ligand isoform X1 [Rattus norvegicus],” Jan. 21, 2021, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006256323.1, “Icos ligand isoform X2 [Rattus norvegicus],” Jan. 21, 2021, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006256324.1, “Icos ligand isoform X3 [Rattus norvegicus],” Jan. 21, 2021, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006496201.1, “inducible T-cell costimulator isoform X1 [Mus musculus],” Sep. 21, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006496202.1, “inducible T-cell costimulator isoform X1 [Mus musculus],” Sep. 21, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006496203.1, “inducible T-cell costimulator isoform X2 [Mus musculus],” Sep. 21, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006538787.3, “tumor necrosis factor receptor superfamily member 4 isoform X1 [Mus musculus],” Sep. 21, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_006710681.1, “tumor necrosis factor receptor superfamily member 9 isoform X1 [Homo sapiens],” Apr. 5, 2022, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_007964137.1, “inducible T-cell costimulator [Chlorocebus sabaeus],” Dec. 1, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_008762504.1, “tumor necrosis factor receptor superfamily member 9 isoform X1 [Rattus norvegicus],” Jan. 21, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_008765300.1, “T-cell-specific surface glycoprotein CD28 isoform X1 [Rattus norvegicus],” Jan. 21, 2021, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_008765358.1, “inducible T-cell costimulator isoform X1 [Rattus norvegicus],” Jan. 21, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_008844474.1, “T-cell-specific surface glycoprotein CD28 [Nannospalax galili],” Jun. 24, 2019, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_008997520.1, “inducible T-cell costimulator [Callithrix jacchus],” Jul. 4, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_010334714.1, “inducible T-cell costimulator isoform X2 [Saimiri boliviensis boliviensis],” Feb. 12, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_010350939.1, “inducible T-cell costimulator [Rhinopithecus roxellana],” Sep. 25, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_010375483.1, “tumor necrosis factor receptor superfamily member 4 [Rhinopithecus roxellana],” Sep. 25, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_010618177.1, “tumor necrosis factor receptor superfamily member 9 isoform X1 [Fukomys damarensis],” Apr. 23, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011248530.1, “tumor necrosis factor receptor superfamily member 9 isoform X1 [Mus musculus],” Sep. 21, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011510496.1, “T-cell-specific surface glycoprotein CD28 isoform X1 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_011510497.1, “T-cell-specific surface glycoprotein CD28 isoform X2 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_011510499.1, “T-cell-specific surface glycoprotein CD28 isoform X3 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_011540376.1, “tumor necrosis factor receptor superfamily member 4 isoform X1 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_011540377.1, “tumor necrosis factor receptor superfamily member 4 isoform X2 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_011540378.1, “tumor necrosis factor receptor superfamily member 4 isoform X3 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_011540379.1, “tumor necrosis factor receptor superfamily member 4 isoform X4 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_011716285.1, “inducible T-cell costimulator isoform X1 [Macaca nemestrina],” Apr. 24, 2018, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011716287.1, “inducible T-cell costimulator isoform X2 [Macaca nemestrina],” Apr. 24, 2018, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011768627.1, “tumor necrosis factor receptor superfamily member 4 [Macaca nemestrina],” Apr. 24, 2018, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011805287.1, “Predicted: inducible T-cell costimulator isoform X1 [Colobus angolensis palliatus],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011805288.1, “Predicted: inducible T-cell costimulator isoform X2 [Colobus angolensis palliatus],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011811769.1, “Predicted: tumor necrosis factor receptor superfamily member 4 [Colobus angolensis palliatus],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011847866.1, “Predicted: inducible T-cell costimulator isoform X1 [Mandrillus leucophaeus],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011847867.1, “Predicted: inducible T-cell costimulator isoform X2 [Mandrillus leucophaeus],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011857387.1, “Predicted: tumor necrosis factor receptor superfamily member 4 [Mandrillus leucophaeus],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011886512.1, “Predicted: tumor necrosis factor receptor superfamily member 4 isoform X1 [Cercocebus atys], ” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011886513.1, “Predicted: tumor necrosis factor receptor superfamily member 4 isoform X2 [Cercocebus atys],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_011903009.1, “Predicted: inducible T- cell costimulator [Cercocebus atys],” Mar. 30, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_012301784.1, “inducible T-cell costimulator isoform X1 [Aotus nancymaae],” Jun. 28, 2017, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_012301785.1, “inducible T-cell costimulator isoform X2 [Aotus nancymaae],” Jun. 28, 2017, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_012865504.1, “Predicted: T-cell-specific surface glycoprotein CD28 [Dipodomys ordii],” Jun. 26, 2015, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_012867363.1, “Predicted: inducible T- cell costimulator isoform X1 [Dipodomys ordii], ” Jun. 26, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_012867370.1, “Predicted: inducible T- cell costimulator isoform X2 [Dipodomys ordii],” Jun. 26, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_012888584.1, “Predicted: tumor necrosis factor receptor superfamily member 9 [Dipodomys ordii],” Jun. 26, 2015, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_012929934.1, “inducible T-cell costimulator isoform X2 [Heterocephalus glaber],” May 23, 2017, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_014966207.1, “T-cell-specific surface glycoprotein CD28 isoform X1 [Macaca mulatta],” Apr. 26, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_016857720.1, “tumor necrosis factor receptor superfamily member 4 isoform X2 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_016857721.1, “tumor necrosis factor receptor superfamily member 4 isoform X4 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_016881773.1, “transmembrane and immunoglobulin domain-containing protein 2 isoform X1 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_017392362.1, “inducible T-cell costimulator [Cebus imitator],” Nov. 20, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_017457364.1, “Icos ligand isoform X4 [Rattus norvegicus],” Jan. 21, 2021, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_017739861.1, “Predicted: inducible T- cell costimulator [Rhinopithecus bieti],” Aug. 24, 2016, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_017750744.1, “Predicted: tumor necrosis factor receptor superfamily member 4 [Rhinopithecus bieti], ” Aug. 24, 2016, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_017802331.1, “inducible T-cell costimulator isoform X3 [Papio anubis],” Nov. 20, 2019, 1 page. [cited by applicant]

GenBank NCBI Reference Sequence: XP_019061859.2, “T-cell-specific surface glycoprotein CD28 [Fukomys damarensis],” Apr. 23, 2020, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021017102.2, “tumor necrosis factor receptor superfamily member 4 [Mus caroli],” Jun. 10, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021027481.1, “T-cell-specific surface glycoprotein CD28 [Mus caroli], ” Jun. 10, 2019, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021030282.1, “inducible T-cell costimulator [Mus caroli],” Jun. 10, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021052880.1, “inducible T-cell costimulator [Mus pahari],” Jun. 18, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021054806.1, “T-cell-specific surface glycoprotein CD28 [Mus pahari],” Jun. 18, 2019, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021056714.1, “tumor necrosis factor receptor superfamily member 4 [Mus pahari],” Jun. 18, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021099219.1, “tumor necrosis factor receptor superfamily member 9 [Heterocephalus glaber],” May 23, 2017, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021119236.1, “inducible T-cell costimulator isoform X1 [Heterocephalus glaber],” May 23, 2017, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021523144.1, “Low Quality Protein: tumor necrosis factor receptor superfamily member 4 [Aotus nancymaae],” Jun. 28, 2017, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_021779593.1, “inducible T-cell costimulator isoform X1 [Papio anubis],” Nov. 20, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_023075099.1, “inducible T-cell costimulator isoform X1 [Piliocolobus tephrosceles],” Dec. 30, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_023075107.1, “inducible T-cell costimulator isoform X2 [Piliocolobus tephrosceles],” Dec. 30, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_024307127.1, “transmembrane and immunoglobulin domain-containing protein 2 isoform X2 [ [cited by applicant]

GenBank NCBI Reference Sequence: XP_025242473.1, “tumor necrosis factor receptor superfamily member 4 [Theropithecus gelada],” Jun. 29, 2018, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_025260986.1, “inducible T-cell costimulator isoform X1 [Theropithecus gelada],” Jun. 29, 2018, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_025260987.1, “inducible T-cell costimulator isoform X2 [Theropithecus gelada],” Jun. 29, 2018, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_025260988.1, “inducible T-cell costimulator isoform X3 [Theropithecus gelada],” Jun. 29, 2018, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_026313228.1, “tumor necrosis factor receptor superfamily member 4 isoform X1 [Piliocolobus tephrosceles],” Dec. 30, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_026313229.1, “tumor necrosis factor receptor superfamily member 4 isoform X2 [Piliocolobus tephrosceles],” Dec. 30, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_029334968.1, “inducible T-cell costimulator [Mus caroli],” Jun. 10, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_029414154.1, “tumor necrosis factor receptor superfamily member 9 isoform X1 [Nannospalax galili],” Jun. 24, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_029414155.1, “tumor necrosis factor receptor superfamily member 9 isoform X1 [Nannospalax galili],” Jun. 24, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_029425757.1, “inducible T-cell costimulator [Nannospalax galili],” Jun. 24, 2019, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_030104805.1, “T-lymphocyte activation antigen CD80 isoform X2 [Mus musculus],” Sep. 21, 2020, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_032134413.1, “inducible T-cell costimulator isoform X1 [Sapajus apella],” Feb. 2, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_032134414.1, “inducible T-cell costimulator isoform X2 [Sapajus apella],” Feb. 2, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_032755445.1, “T-cell-specific surface glycoprotein CD28 [Rattus rattus],” Mar. 14, 2020, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_032755449.1, “inducible T-cell costimulator [Rattus rattus],” Mar. 14, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_033086489.1, “inducible T-cell costimulator [Trachypithecus francoisi],” Mar. 28, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_034354910.1, “T-cell-specific surface glycoprotein CD28 [Arvicanthis niloticus],” May 16, 2020, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_036012281.1, “T-cell-specific surface glycoprotein CD28 isoform X1 [Mus musculus],” Sep. 21, 2020, 3 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_036015651.1, “T-lymphocyte activation antigen CD80 isoform X1 [Mus musculus],” Sep. 21, 2020, 2 pages. [cited by applicant]

GenBank NCBI Reference Sequence: XP_038940099.1, “inducible T-cell costimulator isoform X3 [Rattus norvegicus],” Jan. 21, 2021, 2 pages. [cited by applicant]

Gongbo Li et al., “4-1BB enhancement of CAR T function requires NF-κB and TRAFs,” JCI Insight, Sep. 20, 2018, 3(18):e121322, 19 pages. [cited by applicant]

Guedan, et al., “Engineering and Design of Chimeric Antigen Receptors.” Mol Ther Methods Clin Dev. Dec. 31, 2018, 12:145-156. [cited by applicant]

Guedan, et al., “Enhancing CAR T cell persistence through ICOS and 4-1BB costimulation.” JCI Insight. Jan. 11, 2018, 3(1):e96976, 18 pages. [cited by applicant]

Guo, R et al. “Targeting BCMA to Treat Multiple Myeloma: Updates From the 2021 ASH Annual Meeting,” Front Immunol., Mar. 7, 2022, 13:839097, 19 pages. [cited by applicant]

Hoogi S., et al., “A TIGIT-based chimeric co-stimulatory switch receptor improves T-cell anti-tumor function.” J Immunother Cancer., Sep. 9, 2019, 7(1):243, 13 pages. [cited by applicant]

International Search Report and Written Opinion issued in PCT/US2022/011103 dated Apr. 28, 2022, 1-10. [cited by applicant]

June, C.H., et al., “CAR T cell immunotherapy for human cancer.” Science, Mar. 23, 2018, 359(6382):1361-1365. [cited by applicant]

Klippel, Z.K., et al., “Immune escape from NY-ESO-1-specific T-cell therapy via loss of heterozygosity in the MHC.” Gene Ther. Mar. 2014, 21(3):337-342. Epub Jan. 23, 2014 (14 pages total). [cited by applicant]

Kobold, S., et al., Impact of a New Fusion Receptor on PD-1-Mediated Immunosuppression in Adoptive T Cell Therapy. J Natl Cancer Inst. Jun. 23, 2015, 107(8):djv146, 10 pages. [cited by applicant]

Lee, L. et al. “Evaluation of B cell maturation antigen as a target for antibody drug conjugate mediated cytotoxicity in multiple myeloma,” Br. J. Haematol, 2016, 174:911-922. [cited by applicant]

Li, Y., et al. “Directed evolution of human T-cell receptors with picomolar affinities by phage display.” Nature Biotechnology, Mar. 2005, 23(3):349-354. [cited by applicant]

Liu, X. et al. “A Chimeric Switch-Receptor Targeting PD1 Augments the Efficacy of Second-Generation CAR T Cells in Advanced Solid Tumors,” Cancer Res. Mar. 15, 2016, 76(6):1578-1590. [cited by applicant]

Mackall, C., et al., “Autologous genetically engineered NY-ESO-1 [cited by applicant]

Mackay, M., et al., “The therapeutic landscape for cells engineered with chimeric antigen receptors.” Nat Biotechnol., 2020, 38(2):233-244, including Methods and Reporting Summary (16 total pages). [cited by applicant]

Moon, E.K., et al., “Blockade of Programmed Death 1 Augments the Ability of Human T Cells Engineered to Target NY-ESO-1 to Control Tumor Growth after Adoptive Transfer.” Clin Cancer Res., Jan. 15, 2016, 22(2):436-447. [cited by applicant]

O'donnell, U.S., et al., “Cancer immunoediting and resistance to T cell-based immunotherapy.” Nat Rev Clin Oncol., Mar. 2019, 16(3):151-167. [cited by applicant]

Parmar H.B., et al., “Polybasic Trafficking Signal Mediates Golgi Export, ER Retention or ER Export and Retrieval Based on Membrane-Proximity.” PLoS One. Apr. 2014, 9(4):e94194, 10 pages. [cited by applicant]

Rapoport, A. P. et al., “NY-ESO-1-specific TCR-engineered T cells mediate sustained antigen-specific antitumor effects in myeloma,” Nature Medicine, Aug. 2015, 21(8):914-921 (including online methods, 10 total pages). [cited by applicant]

Raza, A., et al., “Unleashing the immune response to NY-ESO-1 cancer testis antigen as a potential target for cancer immunotherapy.” J Transl Med., Mar. 27, 2020, 18(1):140, 11 pages. [cited by applicant]

Robbins, P. F. et al., “A Pilot Trial Using Lymphocytes Genetically Engineered with an NY-ESO-1-Reactive T-cell Receptor: Long-term Follow-up and Correlates with Response,” Clin Cancer Res, Mar. 2015, 21(5):1019-1027. [cited by applicant]

UniProtKB/Swiss-Prot No. P10747.1, “RecName: Full=T-cell-specific surface glycoprotein CD28; AltName: Full=TP44; AltName: CD_antigen=CD28; Flags: Precursor,” May 25, 2022, 9 pages. [cited by applicant]

UniProtKB/Swiss-Prot No. P15725.1, “RecName: Full=Tumor necrosis factor receptor superfamily member 4; AltName: Full=MRC OX40; AltName: Full=OX40 antigen; AltName: Full=OX40L receptor; AltName: CD_antigen=CD134; Flags: … [cited by applicant]

UniProtKB/Swiss-Prot No. P20334-1, “TNR9_MOUSE,” downloaded from web at https://glygen.org/protein/P20334, only Jul. 13, 2022, 8 pages. [cited by applicant]

UniProtKB/Swiss-Prot No. P31041.2, “RecName: Full=T-cell-specific surface glycoprotein CD28; AltName: CD_antigen=CD28; Flags: Precursor,” May 25, 2022, 5 pages. [cited by applicant]

UniProtKB/Swiss-Prot No. P31042.1, “ RecName: Full=T-cell-specific surface glycoprotein CD28; AltName: CD_antigen=CD28; Flags: Precursor,” May 25, 2022, 4 pages. [cited by applicant]

UniProtKB/Swiss-Prot No. P43489.1, “RecName: Full=Tumor necrosis factor receptor superfamily member 4; AltName: Full=ACT35 antigen; AltName: Full=OX40L receptor; AltName: Full=TAX transcriptionally-activated glycoprotei… [cited by applicant]

UniProtKB/Swiss-Prot No. P47741.1, “ RecName: Full=Tumor necrosis factor receptor superfamily member 4; AltName: Full=OX40 antigen; AltName: Full=OX40L receptor; AltName: CD_antigen=CD134; Flags: Precursor,” May 25, 202… [cited by applicant]

UniProtKB/Swiss-Prot No. Q07011, “TNR9_HUMAN,” downloaded from web at https://www.uniprot.org/uniprotkb/Q07011/entry, on Jul. 13, 2022, 8 pages. [cited by applicant]

UniProtKB/Swiss-Prot No. Q96BF3.2, “RecName: Full=Transmembrane and immunoglobulin domain-containing protein 2; AltName: Full=CD28 homolog; AltName: Full=Immunoglobulin and proline-rich receptor 1; Short=IGPR-1; Flags: … [cited by applicant]

UniProtKB/Swiss-Prot No. Q9R1T7.1, “RecName: Full=Inducible T-cell costimulator; AltName: Full=Activation-inducible lymphocyte immunomediatory molecule; AltName: CD_antigen=CD278; Flags: Precursor,” May 25, 2022, 3 page… [cited by applicant]

UniProtKB/Swiss-Prot No. Q9WVS0.2, “RecName: Full=Inducible T-cell costimulator; AltName: Full=Activation-inducible lymphocyte immunomediatory molecule; AltName: Full=CD28 and CTLA-4-like protein; Short=CCLP; AltName: F… [cited by applicant]

UniProtKB/Swiss-Prot No. Q9Y6W8.1, “RecName: Full=Inducible T-cell costimulator; AltName: Full=Activation-inducible lymphocyte immunomediatory molecule; AltName: CD_antigen=CD278; Flags: Precursor,” May 25, 2022, 5 page… [cited by applicant]

Wang, X et al. “A transgene-encoded cell surface polypeptide for selection, in vivo tracking, and ablation of engineered cells” Blood, Aug. 4, 2011, 118(5):1255-1263. [cited by applicant]

Zhao, Y., et al., “High-Affinity TCRs Generated by Phage Display Provide CD4+ T Cells with the Ability to Recognize and Kill Tumor Cell Lines.” J Immunol., 2007, 179(9):5845-5854. [cited by applicant]

Zhao, Z. et al., “Structural design of engineered costimulation determines tumor rejection kinetics and persistence of CAR T cells,” Cancer cell, Oct. 12, 2015, 28(4):415-428 (27 pages total). [cited by applicant]

Zhong X-S., et al., “Chimeric Antigen Receptors Combining 4-1BB and CD28 Signaling Domains Augment Plskinase/AKT/Bcl-X [cited by applicant]

Feucht, J. et al. “Calibration of CAR activation potential directs alternative T cell fates and therapeutic potency,” Nature Medicine, Jan. 2019, 25:82-88 (28 pages total). [cited by applicant]

International Search Report and Written Opinion for PCT Application No. PCT/US2023/069612 dated Oct. 23, 2023, 21 pages. [cited by applicant]

Li et al., “4-1BB enhancement of CAR T function requires NF-κB and TRAFs”, JCI Insight., Sep. 20, 2018, 3(18):e121322, 43 pages. [cited by applicant]

Macleod et al., “Integration of a CD19 CAR into the TCR Alpha Chain Locus Streamlines Production of Allogeneic Gene-Edited CAR T Cells”, Molecular Therapy, 2017, 25(4):949-961 (24 pages total). [cited by applicant]

Fujiwara et al., “Structure of the Signal Transduction Domain in Second-Generation CAR Regulates the Input Efficiency of CAR Signals,” Int. J. Mol. Sci. 2021, 22, 2476, p. 1-20 and supplementary p. 1-9. Published Mar. 1… [cited by applicant]

Li et al., “Chimeric Antigen Receptor Designed to Prevent Ubiquitination and Downregulation Showed Durable Antitumor Efficacy,” Immunity, 2020; 53: 456-470, el-e6, supplemental p. 23-36. [cited by applicant]

UniProtKB—P20963 (CD3Z_HUMAN). T-cell surface glycoprotein CD3 zeta chain; 12 pages; retrieved on May 13, 2016 from http://www.uniprot.org/uniproUP2. [cited by applicant]