Provectus Head and Neck Cancer Poster Presentation at 2024 American Association for Cancer Research Annual Meeting
Provectus Head and Neck Cancer Poster Presentation at 2024 American Association for Cancer Research Annual Meeting
AACR poster title: “PV 10 induces endoplasmic reticulum stress and autophagy, triggering immunogenic cell death and anti-tumor immunity in head and neck squamous cell carcinoma”
On Thursday, March 7th, Provectus announced that data from preclinical research on PV-10 (rose bengal sodium) for the treatments of human papillomavirus (“HPV”)-positive and HPV-negative head and neck squamous cell carcinoma (“HNSCC”) will be presented at the upcoming annual meeting of the American Association for Cancer Research (“AACR”), to be held April 5-10, 2024 in San Diego, California.
“…a group of malignancies, involving the oral cavity, pharynx, hypopharynx, larynx, nasal cavity, and salivary glands, that together compose the seventh most common cancer diagnosis worldwide. With 890,000 new cases and 450,000 deaths annually per GLOBOCAN estimates, HNSCC accounts for roughly 4.5% of cancer diagnoses and deaths.” (Barsouk et al. 2023)
The work underlying this poster presentation is part of self-funded research that has been conducted by Christine Chung, M.D., Chair, Department of Head and Neck-Endocrine Oncology and Program Leader of Head and Neck Oncology and members of the Chung laboratory at Moffitt Cancer Center (“Moffitt”) in Tampa, Florida since about 2019. Among other achievements, Dr. Chung has been a co-chair of the National Cancer Institute (“NCI”) Head and Neck Steering Committee.
Moffitt’s abstract, which was accepted for a poster presentation, is titled PV 10 induces endoplasmic reticulum stress and autophagy, triggering immunogenic cell death and anti-tumor immunity in head and neck squamous cell carcinoma (Abstract #6742, Topic Track: Immunology, Session: Vaccines, Antigens, and Antigen Presentation 2). You can read the abstract here.
Dr. Shari Pilon-Thomas at Moffitt
Early, arms-length, foundational preclinical, translational, and clinical-mechanism research on PV-10 for Provectus and, consequentially, at and around Moffitt came from Shari Pilon-Thomas, Ph.D. (“SPT”) and her SPT Lab starting in approximately 2011. Numerous presentations by SPT et al. about their PV-10 research were made at the annual meetings of most major cancer conferences, such as the Society of Surgical Oncology (“SSO”), the American Association for Cancer Research (“AACR”), the American Society of Clinical Oncology (“ASCO”), and the Society for Immunotherapy of Cancer (“SITC”). The SPT Lab also published several peer-reviewed papers on PV-10 and have been involved in several of the Company’s clinical trials doing immune correlative work.
As an aside, SPT’s research focus has been on the enhancement of anti-tumor immune responses through the use of vaccines or adoptive cell therapy (“ACT”) with tumor infiltrating lymphocytes (“TIL”) for the treatment of solid tumors. SPT garnered an important reputational win when the FDA granted accelerated approval in refractory metastatic melanoma to TIL therapy lifileucel (Amtagvi by Iovance Biotherapeutics) in February 2024. You can read about Moffitt’s involvement in lifileucel’s development and approval here. ACT, such as TIL, “harvests naturally occurring T cells that have already infiltrated patients’ tumors, and then activates and expands them. Then, large numbers of these activated T cells are re-infused into patients, where they can then seek out and destroy tumors” (Source).
As an aside of this aside, PV-10 injection into a patient’s tumors is akin to in situ vaccination.
Dr. Christine Chung at Moffitt
2019. Dr. Chung approached us in 2019 because she wanted to seek grant funding for an investigator-initiated clinical trial (“IIT”) of PV-10 in oral HNSCC. At the time, her lab had self-funded the evaluation of the immune modulation of PV-10 using HNSCC in vivo models, in collaboration with SPT. Dr. Chung’s concept was to run a clinical trial in parallel with her lab’s mouse study to generate preclinical data that could be validated (or not) by the IIT. Later that same year, Dr. Chung decided to hold off pursuing the IIT until she had generated more preclinical data (and because the funding mechanism was not appropriate for what she had in mind).
2021. We checked in with Dr. Chung in 2021 about her preclinical research. The in vitro and in vivo results, then focused only on HPV-positive HNSCC, were promising, but she felt more work was needed, particularly as it related to the relationship between an injection of PV-10 into the tumor and the subsequent changes in the tumor microenvironment.
2023. The Chung lab reached out to us again in 2023 for more PV-10 drug product to complete a grant-funded continuation of their 2019 work on PV-10 that had then expanded to both HPV-positive and HPV-negative HNSCC.
2024. In addition to their AACR poster presentation, the Chung lab is finalizing a manuscript for near-term submission to a peer-reviewed journal.
Takeaways
The takeaways from Dr. Chung’s work include, but are not limited to:
PV-10 kills yet another tumor type,
PV-10 induces immunogenic cell death in yet another tumor type,
PV-10’s mechanisms of action and immune action, and thus rose bengal sodium’s medical science, have been reproduced yet again in another cancer, and
Key takeaway: We think the Chung lab’s work lends further credence to our belief that PV-10’s innate immune system signaling — the innate immune response that follows PV-10 injection into a patient’s tumor(s) — is akin to a fingerprint, the metaphor for which we use to describe the individuality, identity, specificity, etc. of the information conveyed to the adaptive immune system.
Moffitt’s abstract: “Markers of immunogenic cell death (ICD), including a statistically significant increase in the release of damage-associated molecular pattern molecules HMGB1 and ATP, as well as enhanced surface expression of calreticulin, HSP-70, and HSP-90, were observed.”
We first introduced this takeaway to readers in our June 3, 2023 Provectus Substack titled Cancer Immunotherapy PV-10's Innate Immune Signaling.
We plan to gauge Dr. Chung’s interest in an HNSCC IIT later this year.1
According to Merck & Co., “87% of people who received KEYTRUDA and chemotherapy (244 out of 281 people) had their cancer spread, grow, or get worse compared to 91% of people who received standard treatment (253 out of 278 people). Half of the people who received KEYTRUDA and chemotherapy were alive for 4.9 months without their cancer spreading, growing, or getting worse, compared to 5.1 months for people who received standard treatment.”