ANTI-TUMOR COMBINATION THERAPY COMPRISING ANTI-CD19 ANTIBODY AND GAMMA DELTA T-CELLS
The present disclosure is directed to a combination therapy comprising an anti-CD19 antibody or antibody fragment thereof and gamma delta T-cells (γδ T-cells) for use in the treatment of leukemia or lymphoma.
1 : A method for treatment of hematological cancer, said method comprising administering an anti-CD19 antibody or antibody fragment thereof in combination with γδ T-cells.
2 : The method of to claim 1 wherein said γδ T-cells comprise an enriched γδ T-cell population.
3 : The method of claim 1 wherein said γδ T-cells comprise non-engineered or engineered γδ T-cells and/or admixtures thereof.
4 : The method of claim 1 wherein said γδ T-cells are isolated from peripheral blood, tumor tissue or non-hematopoietic tissue for use in the treatment of cancer.
5 : The method of claim 1 wherein said γδ T-cells are isolated from peripheral blood and were cultivated in the presence of IL-2 and ZOL.
6 : The method of claim 1 wherein said γδ T-cells are blood-derived Vγ9Vδ2 T-cells.
7 : The method of claim 1 wherein the hematological cancer is chronic lymphocytic leukemia (CLL), non-Hodgkin's lymphoma (NHL), small lymphocytic lymphoma (SLL) or acute lymphoblastic leukemia (ALL).
8 : The method of claim 1 wherein said antibody or antibody fragment specific for CD19 and the γδ T-cells are administered in a separate manner.
9 : The method of claim 1 wherein said antibody or antibody fragment specific for CD19 and the γδ T-cells are administered in a simultaneous manner.
10 : The method of claim 1 wherein the anti-CD19 antibody or antibody fragment comprises a heavy chain variable region comprising an HCDR1 region comprising the sequence SYVMH (SEQ ID NO: 1), an HCDR2 region comprising the sequence NPYNDG (SEQ ID NO: 2), and an HCDR3 region comprising the sequence GTYYYGTRVFDY (SEQ ID NO: 3) and a light chain variable region comprising an LCDR1 region comprising the sequence RSSKSLQNVNGNTYLY (SEQ ID NO: 4), an LCDR2 region comprising the sequence RMSNLNS (SEQ ID NO: 5), and an LCDR3 region comprising the sequence MQHLEYPIT (SEQ ID NO: 6).
11 : The method of claim 1 wherein the anti-CD19 antibody or antibody fragment comprises a heavy chain variable region of
(SEQ ID NO: 7)
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIG
YINPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCAR
GTYYYGTRVFDYWGQGTLVTVSS
and a light chain variable region of
(SEQ ID NO: 8)
DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSP
QLLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLE
YPITFGAGTKLEIK.
12 : The method of claim 1 wherein the anti-CD19 antibody comprises a heavy chain of
(SEQ ID NO: 11)
EVQLVESGGGLVKPGGSLKLSCAASGYTFTSYVMHWVRQAPGKGLEWIG
YINPYNDGTKYNEKFQGRVTISSDKSISTAYMELSSLRSEDTAMYYCAR
GTYYYGTRVFDYWGQGTLVTVSSASTKGPSVFPLAPSSKSTSGGTAALG
CLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSSVVTVPSSS
LGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGGPDVE
LFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVQFNWYVDGVEVHNAKTK
PREEQFNSTFRVVSVLTVVHQDWLNGKEYKCKVSNKALPAPEEKTISKT
KGQPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPE
NNYKTTPPMLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYT
QKSLSLSPGK.
13 : The method of claim 1 wherein the anti-CD19 antibody comprises a light chain of
(SEQ ID NO: 12)
DIVMTQSPATLSLSPGERATLSCRSSKSLQNVNGNTYLYWFQQKPGQSP
QLLIYRMSNLNSGVPDRFSGSGSGTEFTLTISSLEPEDFAVYYCMQHLE
YPITFGAGTKLEIKRTVAAPSVFIFPPSDEQLKSGTASVVCLLNNFYPR
EAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLTLSKADYEKHKV
YACEVTHQGLSSPVTKSFNRGEC.
14 : A kit for treatment according to claim 1 , said kit comprising an anti-CD19 antibody or antibody fragment thereof and instructions to administer said anti-CD19 antibody or antibody fragment thereof in combination with γδ T-cells.