Andrew Trinh

Introduction.    Melanoma is a form of skin cancer that arises due to uncontrolled growth of melanocytes¹ and is currently the fifth leading type of cancer in the world. Particularly in the past decade, the incidence of melanoma has significantly risen. Mutations due to radiation from sun exposure is the leading risk factor of getting melanoma². The difficulty in treating this cancer arises in its ability to invade many different skin layers; thus, making it challenging to treat the entirety of the tumor. Malignant melanoma cells have also shown the ability to evade an individual’s immune system through the downregulation of targetable molecules and the amplification of immunosuppressive cytokines³. The combination of these effects led to the development and increased resistance of melanoma in the diseased individuals, eventually increasing the mortality rate for patients. Despite these evasive mechanisms, it has been shown that intratumoral immunotherapy for melanoma can be quite effective for treatment⁴. Here, the utilization of adenovirus and its relation with recombinant cytokines intratumorally are studied. Recombinant cytokines have the capability of altering the tumor microenvironment from within; thereby, working to inhibit the tumor cells from their source^5-7.    Methods.   In this study, melanoma B16 cells expressing ovalbumin were transplanted into immune competent mice. Half of the mice with B16.OVA cells were intratumorally injected with 1 x 10⁹ viral particles of oncolytic adenovirus in combination with 50 μL PBS, while the other half had intratumoral injections of 50 μL PBS. Electronic calipers were utilized every 3 days to measure tumor growth. Flow cytometry was used to measure the proportion of tumor-infiltrating cytotoxic lymphocytes and antitumor CD8⁺ T cells.    Results.   After injection of adenovirus in combination with PBS, the recruitment of immunomodulatory cytokines such as interferon-alpha 2, interferon-gamma, and interluekin-2 rapidly increased⁷. T-cell stimulation also amplified following the recruitment of immunomodulatory cytokines. Evaluation of anergy markers on CD8⁺ tumor infiltrating cells indicate a downregulation of CTLA-4 and PD-1. Regression of tumor size was more greater in mice given intratumoral adenovirus compared to control mice with only PBS⁷.   Conclusion.    In summary, the preclinical results of this treatment have been positive in reducing the tumor’s size and also the tumor’s resistance to cytotoxic CD8⁺ T-cells. The findings described through the inclusion of intratumoral immunotherapy along with T-cell therapies outline a potentially effective treatment option for melanoma and other tumor cells.

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