The enemy is often one we can’t see, and sometimes the enemy is hiding in plain sight. Many dangers avoid detection until it is too late. Cancerous tumors are certainly one such enemy. Matthew Vandermast, President and COO of Oncovir, explains, “So when you have an immunologically cold tumor, it means that the tumor has evaded your body’s base immune system. Cancer has immunologic evasions that allow it to grow unchecked within the body. And what you’ll see in cold tumors is an immunological desert, there aren’t enough immune cells, including T-cells, available in those areas for your body to fight against the cancer.”

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Prostate cancer in situ autovaccination with the intratumoral viral mimic poly-ICLC: Making a cold tumor hot presented by Sujit S. Nair, PhD

PURPOSE To test the safety of sequential intratumoral plus systemic intramuscular injection of poly-ICLC, and its efficacy in priming antitumor immune responses in patients with prostate cancer (PCa).

EXPERIMENTAL PROCEDURES This is an open-label dose-escalating phase 1 neoadjuvant clinical trial of poly-ICLC (NCT03262103) in 12 patients diagnosed with clinically localized PCa with plans to undergo radical prostatectomy (RP). Poly-ICLC was administered intratumorally (Artemis MRI-TRUS-guided) and intramuscularly (e.g., deltoid muscle). Comprehensive transcriptional profiling of tissues, phenotypic and transcriptional analysis of longitudinally collected peripheral blood, and analysis of the prostate tumor microenvironment (TME) were performed before and after poly-ICLC treatment in order to identify innate and adaptive antitumor immune responses within the tumor and in peripheral blood. This trial is the first to use human intratumoral immunotherapy instead of systemic immunomodulation for high-risk PCa patients.

RESULTS Poly-ICLC was well tolerated (safe) in all 12 patients. There were no dose- limiting toxicities or TEAE (treatment-emergent adverse events) withdrawals during treatment. Eight of 10 evaluable patients (80%) had undetectable PSA (<0.1 ng/ml) at 1 year of follow-up post-RP. Eight of 12 evaluable patients (66.7%) and 7 of 10 patients (70%) with biopsy Gleason 8-10 had a lower Gleason score in the post-treatment RP specimen. Transcriptome profiling of paired biopsy and RP specimens showed significant upregulation of gene signatures associated with immune cell infiltration and TP53-associated metabolic genes, but downregulation of gene signatures associated with metastasis and DNA replication. Genes upregulated by poly-ICLC were associated with a good prognosis. Treatment with poly-ICLC increased systemic immune responses, as demonstrated by an increase in cytolytic signatures, T- and NK-cell signatures, and NK-cell subsets in the blood. Multiplex immunohistochemistry analysis revealed a significant increase in the densities of CD4- and CD8-T cells and B cells, as well as evidence of tertiary lymphoid structures (TLS) within the TME of post-treatment RP specimens compared to baseline.

CONCLUSIONS Poly-ICLC treatment can reliably transform the cold TME of PCa into a hot, immune-enhanced ecosystem. The identified baseline and response biomarkers, tertiary lymphoid structures, potential clinical benefit, and immunologic correlates require validation in larger studies.

2024 is poised to be a breakthrough year for Oncovir and Hiltonol. We're thrilled that the L.A. WEEKLY has spotlighted our story, highlighting Hiltonol's significance in both cancer immunotherapy and infectious disease treatment. At Oncovir, our commitment to developing cutting-edge treatments and providing unparalleled support for patients' quality of life remains steadfast. While conquering cancer is undoubtedly challenging and progress often comes in increments, we eagerly anticipate extending our support to more patients and their families in the future. We encourage you to read the article and share it with those who may find it beneficial.

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Oncovir, Inc. President and COO, Matthew Vandermast will be presenting at the on Wednesday, Dec 13th.

New England Venture Summit

Sep 18, 2023 | staff reporter

NEW YORK – Linkinvax on Monday said its partner Gustave Roussy began dosing patients in a Phase I/IIa trial of CD40HVac, a vaccine for HPV-positive oropharyngeal cancer.

CD40HVac comprises a humanized CD40 monoclonal antibody fused to HPV16 E6 and E7 oncoproteins plus Oncovir's Hiltonol (poly-ICLC) immune adjuvant.

The Gustave Roussy cancer center is sponsoring the trial under a January 2023 collaboration agreement with Paris-based Linkinvax. The researchers will assess immunogenicity and safety of the vaccine in patients with HPV-positive oropharyngeal cancer and determine a recommended Phase II dose. To be eligible for the trial, patients' tumors must test positive for HPV16 via a polymerase chain reaction-based assay.

According to the trial protocol, investigators will recruit up to 24 patients who will be randomized to one of two dosing regimens, out of which 10 will be treated with the vaccine in three injections over 24 weeks and two with placebo. The first dose level group will receive 1 mg CD40Hvac and 1 mg Hiltonol. The second group will receive 3 mg CD40HVac and 1 mg Hiltonol.

The trial includes provisions for serious adverse events. Safety data will be reviewed by an independent safety data monitoring board, and in the case of a grade 3 or higher adverse event within the trial, inclusions in the trial will be suspended and a meeting of the safety monitoring board will be convened. If a grade 5 event occurs, vaccinations will also be halted pending a meeting of the board.

The trial's primary objectives are immunological outcomes as determined by the percentage of HPV16-specific T cells present 24 hours after vaccination and identification of a safe and effective dose to recommend for Phase II studies. Exploratory objectives of the study include progression-free and overall survival.

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NCI supported trials study efficacy and safety of Poly ICLC in indications including Breast Cancer, LGG, Melanoma, and Pancreatic Cancer.

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Conference on Retroviruses and Opportunistic Infections

Presented by Yves Levy of the Vaccine Research Institute / INSERM

February 19-22, 2023 | Seattle, Washington

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This study evaluated the safety and tolerability of nasally (in to the nose) administered Poly ICLC treatment in study participants who are at high-risk for COVID-19.

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Poly-ICLC could be a valuable tool to enhance immunotherapeutic approaches for glioblastoma. We conclude by proposing several promising combination strategies that might advance glioblastoma immunotherapy and discuss key pre-clinical aspects to improve clinical translation.

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Findings unraveled the significance of studying tumor biobank tissues, which suggests PKR and OAS as precision oncological suppressor candidates to be targeted by this novel Hiltonol+++ cocktail which represents a prospective drug for development into a potent and tailored therapy for NSCLC subtypes.

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Radio-immunotherapy combination strategy, aimed at resembling viral infection in tumor tissue in combination with a dendritic-cell vaccine and SABR, is safe and shows immune-associated activity and signs of preliminary clinical efficacy.

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