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Updated: Apr 27, 2026
Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine
Published on: February 24, 2023
Systemic administration of platelets incorporating inactivated Sendai virus eradicates melanoma in mice
Tomoyuki Nishikawa1, Li Yu Tung1, Yasufumi Kaneda1
1Division of Gene Therapy Science, Osaka University Graduate School of Medicine, Osaka, Japan.
Abstract:
Tumor microenvironments include a number of fibrin clots due to the microbleeding caused by cancer cell invasion into blood vessels, which suggests the potential utility of a platelet vector for systemic cancer treatment. We previously reported that inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) activates anti-tumor immunity and induces cancer cell-selective apoptosis. The hemagglutination activity that blocks the systemic administration of HVJ-E was dramatically attenuated by incorporation into platelets. Platelets incorporating HVJ-E (PH complex) were then injected into the tail veins of B16F10 melanoma-bearing mice. The PH complex primarily accumulated in tumor tissues and caused the significant accumulation of various immune cells in the tumor bed. Injections of the PH complex to the melanoma-bearing mouse significantly reduced the tumor size, and the tumor growth was ultimately arrested. Secretion of the chemokine regulated upon activation normal T-expressed and presumably secreted (RANTES) was upregulated following PH stimulation. The RANTES-depletion in melanoma-bearing mice significantly attenuated the cytotoxic T lymphocyte activity and led to a dramatic abrogation of the mouse melanoma suppression induced by the PH complex. Thus, a platelet vector incorporating viral particles, a Trojan horse for cancer treatment, will provide a new approach for cancer therapy using oncolytic viruses.
Insights
Platelets carrying inactivated Sendai virus (HVJ-E) effectively target tumors, activating anti-tumor immunity and halting melanoma growth in mice. This platelet-viral complex acts as a Trojan horse for novel cancer therapy.
Area of Science:
- Oncology
- Immunology
- Virology
Background:
- Tumor microenvironments often contain fibrin clots from cancer cell invasion.
- Inactivated Sendai virus (hemagglutinating virus of Japan; HVJ) envelope (HVJ-E) shows potential for anti-tumor immunity and cancer cell apoptosis.
- HVJ-E's hemagglutination activity limits its systemic use.
Purpose of the Study:
- To investigate the efficacy of platelets incorporating HVJ-E (PH complex) as a targeted delivery system for cancer therapy.
- To evaluate the anti-tumor effects and immune responses induced by the PH complex in a melanoma mouse model.
Main Methods:
- HVJ-E was incorporated into platelets to form the PH complex.
- The PH complex was administered intravenously to B16F10 melanoma-bearing mice.
- Tumor growth, immune cell infiltration, and chemokine (RANTES) levels were assessed.
Main Results:
- PH complex accumulated primarily in tumor tissues.
- Significant accumulation of immune cells and upregulation of RANTES were observed in tumors.
- PH complex treatment led to significant tumor size reduction and growth arrest.
- RANTES depletion abrogated the anti-tumor effect and cytotoxic T lymphocyte activity.
Conclusions:
- Platelets serve as effective vectors for delivering viral agents like HVJ-E, overcoming administration limitations.
- The PH complex demonstrates significant anti-melanoma efficacy by enhancing anti-tumor immunity and RANTES secretion.
- Platelet-viral complexes represent a promising "Trojan horse" strategy for oncolytic virus-based cancer therapy.
