Methods and Compositions for Treating Cancer
Through Enhancing Immune Response, Blocking Monocyte Migration, Amplifying Vaccine Immunity and Inhibiting Tumor Growth and Metastasis
Figure 1. Tumor tissues from a vaccinated mouse (right) and a vaccinated plus ondansetron-treated mouse (left) were evaluated using immunohistochemistry to quantitate the numbers of infiltrating CD11b+ monocyte/macrophages in the tumor tissues. Tumors of mice treated with ondansetron had markedly fewer monocyte/macrophages than tumors of mice that received the vaccine alone.
At A Glance
By administering a combination of an effective amount of antigen, a 5-HT3 antagonist, and an angiotensin II receptor blocker researchers at Colorado State University have developed patented methods for enhancing an immune response, decreasing monocyte recruitment to lymph nodes, amplifying vaccine immunity, and reducing tumor growth or metastasis to treat various cancers.
Various compositions, formulations, and methods (including in conjunction with a vaccine or anti-tumor preparation) have been validated in a multitude of experiments including rodent models and in a dogs with cancer.
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Vaccine adjuvant-induced inflammation augments vaccine immunity in part by recruiting antigen presenting myeloid cells (monocytes and neutrophils) to vaccine draining lymph nodes (LNs). However, recent evidence indicates that monocyte recruitment to LNs suppresses local B cell and T cell activation and proliferation. Lowered immune responses following vaccination can lead to decreased vaccine efficacy.
Moreover, the role of immature and immune suppressive myeloid cells, including neutrophils, monocytes, and tumor-associated macrophages, in promoting the growth of primary tumors is well established. Additionally, myeloid cells, and especially monocytes play an important role in creating favorable conditions for the seeding and growth of tumor metastases in the lungs, in part by establishing the so-called metastatic niche. Inflammatory monocytes recruited in response to tumor-derived signals have been shown to play a key role in promoting the growth of tumor metastases. The major chemokine regulating monocyte recruitment is MCP-1 (CCL2), which signals primarily via activation of the receptor CCR2 expressed principally on inflammatory monocytes.
- Neutralizes immune suppression by blocking tumor and vaccine-induced immune suppressive monocytes
- Utilizes approved, off-patent drug resulting in low development risk
- Significantly slows tumor growth
- Cancer treatment
Regan DP, Chow L, Das S, Haines L, Palmer E, Kurihara JN, Coy JW, Mathias A, Thamm DH, Gustafson DL, Dow SW. Losartan Blocks Osteosarcoma-Elicited Monocyte Recruitment, and Combined With the Kinase Inhibitor Toceranib, Exerts Significant Clinical Benefit in Canine Metastatic Osteosarcoma. Clin Cancer Res. 2022 Feb 15;28(4):662-676. doi: 10.1158/1078-0432.CCR-21-2105. PMID: 34580111; PMCID: PMC8866227.
Regan, Daniel, and Steven Dow. “Manipulation of Innate Immunity for Cancer Therapy in Dogs.” Veterinary Sciences, MDPI, 1 Dec. 2015, www.ncbi.nlm.nih.gov/pmc/articles/PMC5644648/.
Mitchell, Leah A., et al. “Suppression of Vaccine Immunity by Inflammatory Monocytes.” The Journal of Immunology, vol. 189, no. 12, 2012, pp. 5612–5621., doi:10.4049/jimmunol.1202151.
Last updated: April 2022