Granted Patent B2

US 12,403,186 · App. 17/233,124 · Granted Sep 2, 2025

Inventor: Frank Borriello (Winchester, MA)

Assignee: Alloplex Biotherapeutics, Inc.

A61K39/0011A61K39/001129A61K39/001138A61K39/001139A61P35/00C07K14/525C07K14/535C07K16/44C12N5/0693A61K2039/5152A61K2039/5156C07K2317/524C07K2317/53C07K2317/56C07K2317/622C07K2317/72C12N2501/25C12N2501/52

Abstract

Claims (19)

1. An allogeneic tumor cell vaccine used to elicit and stimulate an immune response against a melanoma or prostate cancer comprising:

(1) a clonally-derived variant of a melanoma tumor cell line or a prostate tumor cell line comprising:

(a) two or more stably expressed recombinant membrane-bound immunomodulator molecules selected from the group consisting of an IgG1 peptide, a CD40L peptide, a TNF-alpha peptide, and an Flt-3L peptide; and

(b) a stably expressed recombinant soluble GM-CSF peptide; and

(2) a pharmaceutically acceptable carrier;

wherein the clonally-derived variant of the melanoma tumor cell line or the prostate tumor cell line is proliferation-incompetent;

wherein the clonally-derived variant of the melanoma tumor cell line or the prostate tumor cell line is effective to elicit stimulation of the immune response to a subject's melanoma or prostate cancer, respectively, comprising activation of one or more of T cells, B cells, and dendritic cells as measured by one or more parameters selected from cellular proliferation, cellular subset differentiation, cytokine release profile, and tumor cell lysis that improves overall survival of the subject when compared to a control comprising a non-transfected melanoma tumor cell line or a prostate tumor cell line;

wherein the clonally-derived variant of the melanoma tumor cell line or the prostate tumor cell line expresses the soluble GM-CSF peptide comprising an amino acid sequence as set forth in SEQ ID NO: 13 and two or more of:

(a) the membrane-bound IgG1 immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 45;

(b) the membrane-bound CD40L immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 7;

(c) the membrane-bound form of TNF-alpha immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 11; and

(d) the membrane-bound form of Flt-3L immunomodulator peptide comprising an amino acid sequence as set forth in SEQ ID NO: 14;

wherein the melanoma tumor cell line is SK-MEL2, NIS-G, TRI-G, WIL-G, MRI-H-121B, MRI-H-187, MRI-H-221, or MRI-H-255; and

wherein the prostate tumor cell line is CWR-22, DU145, PC-3/M, PC-3, VCaP, MDA PCa 2b, or LNCaP clone FGC.

2. The allogeneic tumor cell vaccine of claim 1 , wherein the clonally-derived variant of the melanoma tumor cell line or prostate tumor cell line

comprises a membrane-bound chimeric fusion protein comprising a fusion of the CD40L immunomodulator peptide and the TNF-alpha immunomodulator peptide.

3. The allogeneic tumor cell vaccine of claim 2 , wherein the membrane-bound chimeric fusion protein comprises the CD40L immunomodulator peptide as set forth in SEQ ID NO: 9 and the TNF-alpha immunomodulator peptide as set forth in SEQ ID NO: 10.

4. The allogeneic tumor cell vaccine of claim 1 , wherein the stably expressed recombinant membrane-bound immunomodulator molecules in (a) include the membrane-bound form of TNF-alpha immunomodulator peptide with an amino acid sequence as set forth in SEQ ID NO: 11.

5. The allogeneic tumor cell vaccine of claim 1 , wherein the subject includes a member of an animal species of mammalian origin.

Assignments (1)

Continuity (3)

References Cited (400)