Frontiers in Oncology (Nov 2022)
Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy
- Yuguo Zhang,
- Musa Gabere,
- Mika A. Taylor,
- Camila C. Simoes,
- Camila C. Simoes,
- Chelsae Dumbauld,
- Oumar Barro,
- Mulu Z. Tesfay,
- Alicia L. Graham,
- Khandoker Usran Ferdous,
- Alena V. Savenka,
- Jean Christopher Chamcheu,
- Charity L. Washam,
- Duah Alkam,
- Allen Gies,
- Stephanie D. Byrum,
- Matteo Conti,
- Steven R. Post,
- Steven R. Post,
- Thomas Kelly,
- Thomas Kelly,
- Mitesh J. Borad,
- Martin J. Cannon,
- Martin J. Cannon,
- Alexei Basnakian,
- Alexei Basnakian,
- Bolni M. Nagalo,
- Bolni M. Nagalo
Affiliations
- Yuguo Zhang
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Musa Gabere
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN, United States
- Mika A. Taylor
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Camila C. Simoes
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Camila C. Simoes
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Chelsae Dumbauld
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN, United States
- Oumar Barro
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN, United States
- Mulu Z. Tesfay
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Alicia L. Graham
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Khandoker Usran Ferdous
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Alena V. Savenka
- Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Jean Christopher Chamcheu
- School of Basic Pharmaceutical and Toxicological Science, College of Pharmacy, University of Louisiana at Monroe, Monroe, LA, United States
- Charity L. Washam
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Duah Alkam
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Allen Gies
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Stephanie D. Byrum
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Matteo Conti
- Public Health Department, AUSL Imola, Imola, Italy
- Steven R. Post
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Steven R. Post
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Thomas Kelly
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Thomas Kelly
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Mitesh J. Borad
- Department of Molecular Medicine, Mayo Clinic, Rochester, MN, United States
- Martin J. Cannon
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Martin J. Cannon
- Department of Microbiology and Immunology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Alexei Basnakian
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Alexei Basnakian
- Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Bolni M. Nagalo
- Department of Pathology, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- Bolni M. Nagalo
- The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences (UAMS), Little Rock, AR, United States
- DOI
- https://doi.org/10.3389/fonc.2022.1042250
- Journal volume & issue
-
Vol. 12
Abstract
It has long been known that oncolytic viruses wield their therapeutic capability by priming an inflammatory state within the tumor and activating the tumor immune microenvironment, resulting in a multifaceted antitumor immune response. Vaccine-derived viruses, such as measles and mumps, have demonstrated promising potential for treating human cancer in animal models and clinical trials. However, the extensive cost of manufacturing current oncolytic viral products makes them far out of reach for most patients. Here by analyzing the impact of intratumoral (IT) administrations of the trivalent live attenuated measles, mumps, and rubella viruses (MMR) vaccine, we unveil the cellular and molecular basis of MMR-induced anti-cancer activity. Strikingly, we found that IT delivery of low doses of MMR correlates with tumor control and improved survival in murine hepatocellular cancer and colorectal cancer models via increased tumor infiltration of CD8+ granzyme B+ T-cells and decreased macrophages. Moreover, our data indicate that MMR activates key cellular effectors of the host’s innate and adaptive antitumor immunity, culminating in an immunologically coordinated cancer cell death. These findings warrant further work on the potential for MMR to be repurposed as safe and cost-effective cancer immunotherapy to impact cancer patients globally.
Keywords
- live attenuated vaccine
- hepatocellular carcinoma
- colorectal cancer
- measles
- mumps
- rubella (MMR) vaccine
