Metaclipse Therapeutics Corporation is developing novel personalized vaccine immunotherapies for cancer. MembrexTM, a proprietary platform approach tailored to each patient and their specific tumor, consists of ‘membrane vesicles’ prepared from a patient’s tumor tissue that Metaclipse modifies with a ‘protein transfer’ method using proven immunostimulatory proteins. After intradermal administration, these modified vesicles deliver both immunostimulatory proteins, which act as adjuvants, and an array of patient-specific tumor-membrane antigens simultaneously to the immune system. This creates robust tumor-specific immunity that Metaclipse anticipates will destroy and/or suppress the growth of metastatic cancer cells. Our preclinical studies demonstrated that our vaccine immunotherapy acts via T cells and thus potentially inducing immune memory against cancers.
Metaclipse has demonstrated the effectiveness of its proprietary membrane-based tumor-specific immunotherapy in eliminating and/or suppressing the growth of cancer cells in several animal models of cancer. The first indication the Company is pursuing with its personalized cancer therapy is triple negative breast cancer (TNBC). TNBCs represent a class of highly variable tumors, and patients with TNBC have considerable unmet medical need.
The Membrex™approach has several inherent advantages over competitive immunotherapies that utilize whole cells and gene transfer: (1) production of TMVs from a patient’s tumor does not require establishment of immortalized tumor cell lines, T cell cultures or the use of viral vectors; (2) rapid, cost-effective manufacture and administration of the therapy to the patient within 2 weeks; (3) multi-valent immune response generated against all membrane-bound tumor antigens and tumor-specific peptides associated with Major Histocompatibility Complex Class I molecules; and (4) the therapy’s synergy with immune checkpoint blockade inhibitors, enhancing response rates for checkpoint blockade-resistant indications
Clinical, technical, regulatory, and market considerations have guided Metaclipse to select the treatment of certain metastatic head and neck, and lung cancers as subsequent landing indications. Additional vaccine products include a modified influenza vaccine using the membrane-bound adjuvants to enhance immunity in older adults. Metaclipse intends to commercialize its products through licensing agreements with major pharmaceutical companies after establishing safety and effectiveness.
We demonstrated effectiveness of the Membrex™ approach in combination with anti-CTLA-4 antibody in an aggressive, highly metastatic mouse model of TNBC. We also showed that our approach is safe when given alone or in combination with checkpoint inhibitors in an independent GLP toxicology study. We have already participated in a pre-IND meeting with the FDA and expect to enter into Phase I clinical trials in 2022 for metastatic TNBC. We anticipate that our vaccine will be used as a combination therapy with an approved checkpoint blockade inhibitor.
We demonstrated effectiveness of our approach, both alone and in combination with checkpoint blockade, in several mouse head and neck cancer models.
We established efficacy of the approach in combination with checkpoint blockade in a mouse lung cancer model.
Metformin Reduces PD-L1 on Tumor Cells and Enhances the Anti-tumor Immune Response Generated by Vaccine Immunotherapy. Muñoz LE, Huang L, Bommireddy R, Sharma R, Monterroza L, Guin RN, Samaranayake S, Pack CD, Ramachandiran S, Reddy SJC, Shanmugam M, Selvaraj P. J Immunother Cancer, 2021. 9:e002614. doi:10.1136/jitc-2021-002614. PubMed PMID: 34815353; PubMed Central PMCID: PMC8611422
Dendritic cells pulsed with cytokine-adjuvanted tumor membrane vesicles inhibit tumor growth in HER2-Positive and Triple Negative Breast Cancer Models. Muñoz LE, Monterroza L, Bommireddy R, Shafizadeh Y, Pack CD, Ramachandiran S, Reddy SJC, Selvaraj P. International Journal of Molecular Sciences, 2021. 22(16), 8377. PubMed PMID: 34445092; PubMed Central PMCID: PMC8395038
Tumor membrane-based vaccine immunotherapy in combination with anti-CTLA-4 antibody confers protection against immune checkpoint resistant murine triple negative breast cancer. Pack CD, Bommireddy R, Muñoz LE, Patel JM, Bozeman EN, Dey P, Radhakrishnan V, Vartabedian VF, Venkat K, Ramachandiran S, Reddy S JC, Selvaraj P. Human Vaccines & Immunotherapeutics, 2020. DOI: 10.1080/21645515.2020.1754691. PubMed PMID: 32530786
Tumor membrane vesicle vaccine augments the efficacy of anti-PD-1 antibody in immune checkpoint inhibitor-resistant squamous cell carcinoma models of head and neck cancer. Bommireddy R, Muñoz LE, Kumari A, Huang L, Fan Y, Monterroza L, Pack CD, Ramachandiran S, Reddy SJC, Kim J, Chen ZG, Saba NF, Shin DM, Selvaraj P. Vaccines, 2020. 8(2):182. PubMed PMID: 32295135; PubMed Central PMCID: PMC7348725
Therapeutic efficacy of PD-L1 blockade in a breast cancer model is enhanced by cellular vaccines expressing B7-1 and glycolipid-anchored IL-12. Bozeman EN, He S, Shafizadeh Y, Selvaraj P. Human Vaccines & Immunotherapeutics, 2016. 12:421-30. PubMed PMID: 26308597; PubMed Central PMCID: PMC5049731
Plasma membrane vesicles decorated with glycolipid-anchored antigens and adjuvants via protein transfer as an antigen delivery platform for inhibition of tumor growth. Patel JM, Vartabedian VF, Bozeman EN, Caoyonan BE, Srivatsan S, Pack CD, Dey P, D’Souza MJ, Yang L, Selvaraj P. Biomaterials, 2016. 74:231-244. PubMed PMID: 26461116; PubMed Central PMCID: PMC4661141
Expression of membrane anchored cytokines and B7-1 alters tumor microenvironment and induces protective antitumor immunity in a murine breast cancer model. Bozeman EN, Cimino-Mathews A, Machiah DK, Patel JM, Krishnamoorthy A, Tien L, Shashidharamurthy R, Selvaraj P. Vaccine, 2013. 31:2449-56. PubMed PMID: 23541884; PubMed Central PMCID: PMC3686649
Human tumor membrane vesicles modified to express glycolipid-anchored IL-12 by protein transfer induce T cell proliferation in vitro: a potential approach for local delivery of cytokines during vaccination. Nagarajan S, Selvaraj P. Vaccine, 2006. 24:2264-74. PubMed PMID: 16376465
Development of therapeutic vaccines by direct modification of cell membranes from surgically removed human tumor tissue with immunostimulatory molecules. Poloso NJ, Nagarajan S, Bumgarner GW, Selvaraj P. Vaccine, 2001. 19:2029-38. PubMed PMID: 11228374
Protein transfer of glycosyl-phosphatidylinositol-B7-1 into tumor cell membranes: a novel approach to tumor immunotherapy. McHugh RS, Nagarajan S, Wang YC, Sell KW, Selvaraj P. Cancer Research, 1999. 59:2433-7. PubMed PMID: 10344754
Influenza Virus-like Particle-Based Hybrid Vaccine Containing RBD Induces Immunity against Influenza and SARS-CoV-2 Viruses. Bommireddy R, Stone S, Bhatnagar N, Kumari P, Muñoz LE, Oh J, Kim K-H, Berry JTL, Jacobsen KM, Jaafar L, Naing SH, Blackerby AN, Van der Gaag T, Wright CN, Lai L, Pack CD, Ramachandiran S, Suthar MS, Kang SM, Kumar M, Reddy SJC, Selvaraj P. Vaccines, 2022.10: 944. Pubmed PMID: 35746552. PubMed Central PMCID: PMC9230705.
Protein transfer-mediated surface engineering to adjuvantate virus-like nanoparticles for enhanced anti-viral immune responses. Patel JM, Kim MC, Vartabedian VF, Lee YN, He S, Song JM, Choi HJ, Yamanaka S, Amaram N, Lukacher A, Montemagno CD, Compans RW, Kang SM, Selvaraj P. Nanomedicine, 2015.11(5):1097-107. Pubmed PMID: 25752855. PubMed Central PMCID: PMC4512837.
GPI-GM-CSF protein transferred onto H5 influenza VLPs remains stably expressed and functionally active. Patel JM, SH, Amaram N, Yamanaka S, Vartabedian VF, Vijayaraghavan R, Song JM, Shashidharamurthy R, Compans RW, Kang SM and Selvaraj P. The Journal of Immunology 2013. 190:17.
September 2021- Metaclipse Therapeutics is awarded $2 million by the National Cancer Institute (NCI) to support a phase 1 clinical trial to evaluate its personalized immunotherapy platform, Membrex™ for the treatment of metastatic triple negative breast cancer (TNBC), in partnership with Winship Cancer Institute and Emory University.
April 2021- Shaker CR Jakkidi, our President and Co-Founder is awarded the 2021 Golden Helix Community award from Georgia Bio.
June 2020- Metaclipse Therapeutics is awarded $2.2M from the NIAID/NIH to develop a SARS-CoV-2 vaccine for the elderly based on its infectious disease vaccine platform, VaxRex™.