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Adoptive T Cell Therapy for Pancreatic Cancer

Award Number: R01CA237672
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 08/01/2019
PERIOD OF PERFORMANCE END DATE: 07/31/2025

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Adoptive T Cell Therapy for Pancreatic Cancer - Pancreatic cancer will be responsible for over 44,000 deaths in the US this year and is currently the 3rd leading cause of cancer mortality; survival in this disease has not changed in the last 40 years. Although immune checkpoint inhibitors have emerged as highly effective approaches for tumors with high mutational burden, such is not the case with pancreatic cancer which lacks a significant endogenous tumor-reactive T cell population. Adoptively transfer of antigen-specific T cells would provide an effector substrate for immune checkpoint inhibition and we reason that such a combination strategy would be desirable. In this proposal we address two major challenges to advancing the use of adoptive cellular therapy (ACT) for pancreatic cancers: 1. a paucity of proven immunogenic targets for pancreatic cancer and, 2., a means of rapidly deploying antigen-specific cellular therapy targeting such antigens. In this proposal we plan to target a tumor cell-associated target antigen (VCY) and a tumor stroma-associated target (COL6A3), both highly prevalent (> 70% of tumors), and highly immunogenic. Our scientific premise is that strategies that address the lack of tumor-reactive T cells in pancreatic cancer, where the mutational burden and immunogenicity is significantly lower, would be desirable and achievable by the adoptive transfer of tumor-reactive T cells recognizing pancreatic cancer-associated antigens. Adoptive cellular therapy (ACT) is a promising form of immunotherapy that involves the ex vivo isolation and expansion of antigen-specific T cells for infusion. Based on the premise that strategies to extend in vivo persistence of transferred T cells and induce antigen-spreading will lead to improved clinical response following ACT, we hypothesize that adoptive transfer of long-lasting central memory type T cells in combination with PD1 blockade will lead to extended in vivo survival and enhanced activation of endogenous T cells recognizing non-targeted antigens (antigen-spreading). Our ETC (endogenous T cell therapy) approach to ACT was to pioneer a strategy that uses peripheral blood as a source of T cells. Using a combination of IL-21 priming (to enrich for central memory type T cells) and tetramer-guided cell sorting, we can routinely isolate rare tumor-reactive T cells from the peripheral blood ( < 1:100,000) and expand these to a > 20 billion uniformly defined central memory – type specific T cells with defined specificity and high replicative capacity as demonstrated by several prior studies demonstrating months-long in vivo persistence at frequencies 1-10 % commensurate with durable clinical responses. We propose a Phase IB trial targeting COL6A3 and VCY in patients with refractory pancreatic adenocarcinoma, first in a dose escalation cohort, and when a dose has been identified, an expansion cohort in combination with PD1 blockade.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2026 ( Subtotal = -$8,288 )
2026	2023	THE UNIVERISTY OF TEXAS M.D. ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	5	12/8/2025	NON-COMPETING CONTINUATION	-$8,288
														Subtotal = -$8,288

Issue Date FY: 2023 ( Subtotal = $1 )
2023	2023	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	5	9/6/2023	NON-COMPETING CONTINUATION	$1
														Subtotal = $1

Issue Date FY: 2022 ( Subtotal = $613,867 )
2022	2022	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	4	8/18/2022	NON-COMPETING CONTINUATION	$613,867
														Subtotal = $613,867

Issue Date FY: 2021 ( Subtotal = $623,803 )
2021	2021	UNIVERSITY OF TEXAS M. D. ANDERSON CANCER CENTER, THE	1515 HOLCOMBE BLVD	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	3	7/26/2021	NON-COMPETING CONTINUATION	$623,803
														Subtotal = $623,803

Issue Date FY: 2020 ( Subtotal = $773,314 )
2020	2020	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	001	2	9/1/2020	SUPPLEMENT FOR EXPANSION	$149,511
2020	2020	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	2	7/22/2020	NON-COMPETING CONTINUATION	$623,803
														Subtotal = $773,314

Issue Date FY: 2019 ( Subtotal = $623,803 )
2019	2019	UNIVERSITY OF TEXAS M D ANDERSON CANCER CENTER	1515 HOLCOMBE BLVD UNIT 207	HOUSTON	TX	77030	HARRIS	USA	Cancer Treatment Research	000	1	7/25/2019	NEW	$623,803
														Subtotal = $623,803

Grand Total All Awards = $2,626,500

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Adoptive T Cell Therapy for Pancreatic Cancer

Award Number: R01CA237672

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 08/01/2019

PERIOD OF PERFORMANCE END DATE: 07/31/2025

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