Repurposing Live Attenuated Trivalent MMR Vaccine as Cost-effective Cancer Immunotherapy
Frontiers in Oncology(2022)
摘要
Despite its rising promise, cancer immunotherapy remains out of reach for many patients because of the extensive cost of manufacturing immunotherapy products. In this study, we show that intratumoral injections of the trivalent measles, mumps, and rubella (MMR) live attenuated viral vaccine (LAVs) modulates a potent cytotoxic T-cell antitumor immune response, resulting in tumor growth inhibition and improved survival in syngeneic mouse models of hepatocellular carcinoma and colorectal cancer. Using an integrated transcriptomic and proteomic approach, we demonstrated that mechanistically, MMR exerts its antitumor activity by priming innate and adaptive antitumor immune responses, leading to immunologically coordinated cancer cells death. Our findings highlight a promising potential for LAVs, such as MMR, to be repurposed as cost-effective cancer immunotherapy.
### Competing Interest Statement
The authors have declared no competing interest.
* ALP
: alkaline phosphatase
ALT
: alanine aminotransferase
Anti-Measles
: anti-measles fusion and hemagglutinin antibody
Anti-Mumps
: anti-mumps fusion and hemagglutinin antibody
Anti-Rubella
: anti-rubella envelope glycoprotein E
AST
: aspartate aminotransferase
ATCC
: American Tissue Culture Collection
CTLs
: cytotoxic T lymphocytes
CRC
: Colorectal cancer
DMEM
: Dulbecco modified eagle medium
DPBS
: dulbecco phosphate-buffered saline
ELISA
: enzyme-linked immunosorbent assay
G-MDSCs
: granulocytic myeloid-derived suppressor cells
GzmB
: granzyme B
h
: human
HCC
: hepatocellular carcinoma
HGB
: hemoglobin
LAV
: live attenuated viral vaccine
MOI
: multiplicity of infection
PBS
: phosphate-buffered saline
PD-1
: programmed cell death protein 1
PE
: phycoerythrin
RNA
: ribonucleic acid
TAMs
: tumor-associated macrophages
IT
: intratumoral
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