Thursday, April 25, 2024 4/25/2024

CAR T CELLS ENGINEERED TO KILL HIV-INFECTED CELLS WHILE SECRETING BROADLY NEUTRALIZING ANTIBODIES

Award Number: R01AI150381
ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

Group Awards By Issue Date FY or Funding FY:

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PROJECT SUMMARY A cure for HIV requires the elimination of the latently-infected pool of host cells harboring HIV provirus, but this has proven quite difficult and remains a major obstacle in the field. Currently, several chemical latency reversing agents have been described, however, their in vivo efficacy has not been demonstrated. Thus, the need for new approaches to address this issue is urgently needed. One attractive method to combat HIV latency, would be a self-sustaining curative to endlessly surveil the host rapidly killing newly activated reservoir cells before the release of a significant amount of virus. Previously, T cells transduced to express CD4 on their surface linked to activation signaling machinery, chimeric antigen receptor (CAR) T cells, were employed to target and kill infected host cells. But there were substantial drawbacks with this approach, including a novel entry route for infection of CD8 T cells, shielding of the CD4-binding site, and lack of efficacy. Utilizing secreted high-affinity anti-HIV bnAbs, which are remarkably effective across a wide swath of HIV strains, in conjunction with superior CAR designs, we here propose to exploit both advancements to generate doubly immunotherapeutic improved CAR T cells. These pioneering studies will provide new insights into how to access and control the reservoir of latently HIV-infected cells and, in combination with ART, address the exigent goal of functional control of HIV. Upon completion of this project, we expect to have several validated CAR T cell constructs ready for future testing in SHIV non-human primate models and/or perhaps humans. Since these studies utilize autologous T cells, we expect to see very few adverse events. Moreover, if successful, life-long use of anti-retrovirals, which have been associated with toxicity, is likely to be reduced or perhaps eliminated by this approach.


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: 2024 ( Subtotal = $480,000 )
2024	2024	THE SCINTILLON INSTITUTE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	6	3/20/2024	NON-COMPETING CONTINUATION	$480,000
														Subtotal = $480,000

Issue Date FY: 2023 ( Subtotal = $480,000 )
2023	2023	SCINTILLON INSTITUTE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	5	2/16/2023	NON-COMPETING CONTINUATION	$480,000
2023	2020	SCRIPPS RESEARCH INSTITUTE	10550 N TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	10/21/2022	NEW	-$19,072
2023	2020	THE SCINTILLON INSTITUTE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	10/21/2022	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$19,072
														Subtotal = $480,000

Issue Date FY: 2022 ( Subtotal = $480,000 )
2022	2022	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	4	2/25/2022	NON-COMPETING CONTINUATION	$480,000
														Subtotal = $480,000

Issue Date FY: 2021 ( Subtotal = $511,900 )
2021	2021	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	002	3	3/31/2021	NON-COMPETING CONTINUATION	$480,000
2021	2020	SCINTILLON INSTITUTE,THE	6868 NANCY RIDGE DR	SAN DIEGO	CA	92121	SAN DIEGO	USA	Allergy and Infectious Diseases Research	001	2	3/10/2021	CHANGE OF GRANTEE / TRAINING INSTITUTION / AWARDING INSTITUTION	$422,400
2021	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	3/10/2021	NEW	-$390,500
														Subtotal = $511,900

Issue Date FY: 2020 ( Subtotal = $443,750 )
2020	2020	SCRIPPS RESEARCH INSTITUTE, THE	10550 NORTH TORREY PINES RD	LA JOLLA	CA	92037	SAN DIEGO	USA	Allergy and Infectious Diseases Research	000	1	3/25/2020	NEW	$443,750
														Subtotal = $443,750

Grand Total All Awards = $2,395,650

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CAR T CELLS ENGINEERED TO KILL HIV-INFECTED CELLS WHILE SECRETING BROADLY NEUTRALIZING ANTIBODIES

Award Number: R01AI150381

ORGANIZATION: NATIONAL INSTITUTE OF ALLERGY & INFECTIOUS DISEASES

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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