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Cancer therapy with a combination of oncolytic bacteria and virus to enhance targeted cell killing and anti-tumor immune responses

Award Number: R21CA249517
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

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Project Summary/Abstract Cancer is one of the leading causes of death in the United States and worldwide. Appropriate activation of the immune system and effective targeting of tumor cells are the primary hurdles to be overcome for successful cancer immunotherapy. Microbes-based therapy was extensively studied recently to fill the critical unmet needs of cancer patients, where the current treatment options have been exhausted. We have developed genetically engineered Salmonella (GMS), which can actively search for cancer cells, induce tumor regression, prolong survival time, and inhibit cancer metastasis in multiple mouse models. They can also eradicate themselves from the host after treatment. Interestingly, Salmonella also processes multiple natural killer (NK) cell stimulators. On the other hand, oncolytic viruses are new cancer immunotherapeutics and have been approved to use in the clinic. Oncolytic Myxoma virus (MYXV) has been tested in multiple preclinical cancer models and has demonstrated immune stimulating properties for cancer treatment. MYXV was able to bring CD45+ leukocytes to the tumor bed. In addition, these large DNA viruses can be armed to express additional immune activating molecules. In this study, we propose to explore a novel cancer treatment approach that combines the targeted cancer cell killing ability of bacteria and immune stimulating abilities of both oncolytic bacteria and viruses. Apart from the direct killing of cancer cells, improved GMS will stimulate NK cells and MYXV will recruit other tumor-infiltrating leukocytes to activate the anti-tumor immune responses. In addition, we will explore the transgene expressing armed MYXVs that will express cytokines and chemokines to recruit more specific tumor-infiltrating leukocytes. The success of our efforts would turn microbes to appropriate onsite attractors and activators of the immune system for effective cancer therapy to be successful and applicable across a wide range of tumor types.


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: 2022 ( Subtotal = $179,825 )
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Detection and Diagnosis Research	001	2	6/9/2022	NON-COMPETING CONTINUATION	$14,681
2022	2022	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Detection and Diagnosis Research	000	2	11/10/2021	NON-COMPETING CONTINUATION	$165,144
														Subtotal = $179,825

Issue Date FY: 2021 ( Subtotal = $220,193 )
2021	2021	ARIZONA STATE UNIVERSITY	660 S MILL AVE STE 312	TEMPE	AZ	85281	MARICOPA	USA	Cancer Detection and Diagnosis Research	000	1	12/15/2020	NEW	$220,193
														Subtotal = $220,193

Grand Total All Awards = $400,018

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Cancer therapy with a combination of oncolytic bacteria and virus to enhance targeted cell killing and anti-tumor immune responses

Award Number: R21CA249517

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

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