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Controlled Antigen Delivery for Prophylactic Cancer Vaccination

Award Number: K00CA284262
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/01/2023
PERIOD OF PERFORMANCE END DATE: 04/30/2028

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Controlled Antigen Delivery for Prophylactic Cancer Vaccination - ABSTRACT In the United States, cancer is the second leading cause of death, and it is projected that 39.5% of all US adults will be diagnosed with cancer in their lifetimes. Carcinomas comprise up to 90% of all US cancer cases. Chemotherapeutics and antibody immune checkpoint inhibitors (ICIs) are promising treatments for these cancers but are not effective in all cases and exact a large toll on the quality of life of patients due to off-target toxicity. The goal of this proposal is to develop a peptide-based hydrogel therapeutic platform for the local delivery of chemotherapeutics and ICIs to maximize treatment efficacy and mitigate systemic toxicity. Boronic acid-containing small molecule drugs (BACSMs) are a growing class of chemotherapeutics for the treatment of cancer. Bortezomib is an FDA-approved BACSM for the treatment of multiple myeloma and causes immunogenic cancer cell death to help the body develop an anti-cancer immune response. There is interest to expand the use of bortezomib to solid tumors but these efforts face challenges due to the inability to maintain high local concentrations in the tumor without systemic toxicity. Multidomain peptide (MDP) hydrogels are self-adjuvanting materials that have been investigated for cancer immunotherapy and drug delivery. The limitations of bortezomib may be ameliorated by using MDPs hydrogels as a local drug delivery platform by allowing for local intratumoral drug delivery to maximize treatment efficacy while minimizing off-target toxicity. Boronic acids are known to form dynamic covalent bonds with diols, catechols, and salicylhydroxamic acids (SHAs), which I plan to use to control the delivery of anti-cancer BACSMs from hydrogels. In the F99 phase of this proposal, I aim to develop catechol- and SHA-functionalized MDP hydrogels for local bortezomib delivery to improve the efficacy, safety, and accessibility of this chemotherapeutic treatment. I hypothesize that MDP adjuvancy will synergize with bortezomib-induced immunogenic cell death to generate protective anti-cancer immunity in a murine model of head and neck squamous cell carcinoma (HNSCC). These boronic acid-binding MDPs can be used to control the release of any payload that has a boronic acid moiety. Thus, in the K00 phase of this proposal, I aim to modify ICI antibodies with noncanonical boronic acid motifs to fine-tune their release from the designed MDPs. I will use this platform to intratumorally co-deliver bortezomib with immune checkpoint inhibitors to facilitate an anti-cancer immune response in murine models of HNSCC, melanoma, and breast cancer to demonstrate the broad utility of this platform. These materials could help treat patients with malignant tumors and protect them from cancer recurrence after treatment while mitigating side effects associated with chemotherapy and ICIs.


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: 2025 ( Subtotal = $97,672 )
2025	2025	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Research Manpower	000	3	5/19/2025	NON-COMPETING CONTINUATION	$97,672
														Subtotal = $97,672

Issue Date FY: 2024 ( Subtotal = $96,541 )
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Research Manpower	002	2	8/22/2024	EXTENSION WITH OR WITHOUT FUNDS	$0
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Research Manpower	001	2	8/12/2024	EXTENSION WITH OR WITHOUT FUNDS	$7,052
2024	2024	MASSACHUSETTS INSTITUTE OF TECHNOLOGY	77 MASSACHUSETTS AVE	CAMBRIDGE	MA	02139	MIDDLESEX	USA	Cancer Research Manpower	000	2	5/14/2024	EXTENSION WITH OR WITHOUT FUNDS	$89,489
														Subtotal = $96,541

Grand Total All Awards = $194,213

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Controlled Antigen Delivery for Prophylactic Cancer Vaccination

Award Number: K00CA284262

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 09/01/2023

PERIOD OF PERFORMANCE END DATE: 04/30/2028

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