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Personalized vaccine immunotherapy in combination with anti-PD 1 antibody for recurrent or metastatic squamous cell carcinoma of the head and neck

Award Number: R01CA262123
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 04/18/2023
PERIOD OF PERFORMANCE END DATE: 03/31/2028
AWARD TERMINATION DATE: 05/27/2025

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Personalized vaccine immunotherapy in combination with anti-PD 1 antibody for recurrent or metastatic squamous cell carcinoma of the head and neck - PROJECT SUMMARY/ABSTRACT Immune checkpoint inhibitors (ICI) such as anti-PD-1 antibodies, have improved the survival of patients with metastatic head and neck squamous cell carcinoma (HNSCC). However, only a subset (<20%) of patients responds to single agent ICI. Since ICI acts by blocking the negative regulators of pre-existing anti-tumor T cell immunity, the lack of response of the majority of HNSCC patients to anti-PD-1 mAb suggests that most HNSCC patients either do not have pre-existing anti-tumor immunity or that other immunosuppressive pathways play a dominant role. Therefore, combining anti-PD-1 mAb with a vaccination approach that can induce anti-tumor T cell immunity is likely to be more effective than single agent ICI. However, patient-to-patient variation in target antigens makes HNSCC one of the most challenging cancers for developing an effective therapeutic vaccine. To address this, we propose to develop a novel vaccine immunotherapy to treat HNSCC using an approach that is personalized, thus incorporating patient-to-patient variation in antigenic signature. Our autologous therapeutic vaccine consists of tumor membrane vesicles (TMVs) made from the patients’ tumors conjugated to potent immunostimulatory molecules (ISMs) by protein transfer. In contrast to previous autologous tumor lysate vaccines, the tumor antigens are physically linked to ISMs via a TMV scaffold in our vaccines, thus simultaneously presenting the patient’s unique tumor antigen signature and ISMs to the immune cells to induce effective anti-tumor responses. Such a physical linkage of antigens and adjuvants has been shown to induce a more effective immune response than a mixture of unconjugated antigens and adjuvants. Furthermore, unlike whole cell vaccines, TMV vaccines do not secrete immunosuppressive factors. TMVs are particulate in nature and carry membrane associated tumor antigens, altered carbohydrate antigens, and antigenic epitopes derived from cytosolic proteins in the form of major histocompatibility complex associated peptides. Our preliminary studies show that TMV vaccine in combination with ICI is more effective than ICI alone in murine oral cancer models. We hypothesize that a personalized vaccine immunotherapy will expand tumor-specific T cells and the addition of ICI prevents the exhaustion of tumor antigen-specific T cells to induce robust anti-tumor T cell responses and significantly enhance the clinical response against HNSCC tumors that are not responsive to currently approved immunotherapies. The hypothesis will be tested in the following specific aims: Aim 1: To determine whether the dose and schedule can be altered to increase the anti-tumor immune response and efficacy of TMV vaccine in a mouse model of HNSCC, Aim 2: To investigate whether TMV vaccine inhibits metastasis/recurrence and extends the survival of mice in a clinically relevant setting, and Aim 3: To conduct a phase 1b dose-escalation clinical trial of TMV-based immunotherapy alone and in combination with pembrolizumab in patients with recurrent or metastatic HNSCC. Completion of the proposed work will advance a novel, personalized vaccine immunotherapy approach for patients with recurrent and/or metastatic HNSCC.


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 = $619,091 )
2026	2026	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	000	4	4/17/2026	NON-COMPETING CONTINUATION	$619,091
														Subtotal = $619,091

Issue Date FY: 2025 ( Subtotal = $629,482 )
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	000	3	3/10/2025	NON-COMPETING CONTINUATION	$566,534
2025	2025	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	001	3	5/26/2025	NON-COMPETING CONTINUATION	$62,948
2025	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	002	2	5/27/2025	TERMINATION	$0
														Subtotal = $629,482

Issue Date FY: 2024 ( Subtotal = $688,530 )
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	002	2	8/19/2024	SUPPLEMENT FOR EXPANSION	$48,916
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	000	2	2/22/2024	NON-COMPETING CONTINUATION	$575,653
2024	2024	EMORY UNIVERSITY	201 DOWMAN DR NE	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	001	2	4/18/2024	NON-COMPETING CONTINUATION	$63,961
														Subtotal = $688,530

Issue Date FY: 2023 ( Subtotal = $625,507 )
2023	2023	EMORY UNIVERSITY	201 DOWMAN DR	ATLANTA	GA	30322	DEKALB	USA	Cancer Treatment Research	000	1	4/18/2023	NEW	$625,507
														Subtotal = $625,507

Grand Total All Awards = $2,562,610

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Personalized vaccine immunotherapy in combination with anti-PD 1 antibody for recurrent or metastatic squamous cell carcinoma of the head and neck

Award Number: R01CA262123

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 04/18/2023

PERIOD OF PERFORMANCE END DATE: 03/31/2028

AWARD TERMINATION DATE: 05/27/2025

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