1/ $PVCT’s PV-10 (#RoseBengalSodium) Immuno-Oncology Cycle & PD-1-Combination Mechanism. A #THREAD. #InduceAndBoost.
2/ Over the past decade-plus, cancer immunotherapy with antibodies targeting the PD-1 immune checkpoint pathway (i.e., PD-1 inhibitors #PD1) has yielded dramatic improvement in clinical outcome for many patients with #CutaneousMelanoma. #Keytruda #Opdivo #otherPD1s #PDL1s
3/ However, patients with Stage III disease and, in particular, those with in-transit disease (i.e., in-transit melanoma; ITM #IntransitMelanoma), have presented unique challenges with regard to response rate and durability of response.
4a/ A recent international multi-center meta-analysis [fn 1] showed acceptable rates of response (37% CR, 56% ORR in 233 ITM patients treated with PD-1 inhibitors), but this response was not durable (median PFS of 10 months, with approximately half of CR patients experiencing… twitter.com/i/web/status/1…
4b/ [1] Holmberg CJ et al. The efficacy of immune checkpoint blockade for melanoma in-transit with or without nodal metastases - A multicenter cohort study. Eur J Cancer. 2022 Jul;169:210-222. doi.org/10.1016/j.ejca….
5/ $PVCT’s PV-10 (#RoseBengalSodium) is an investigational small-molecule cancer immunotherapy administered to solid tumors by intralesional (IL) injection.
6a/ Rapid internalization of $PVCT’s (#RoseBengalSodium by tumor cells disrupts lysosomal integrity leading to acute autolysis of tumor cells via immunogenic cell death (ICD) that can be evident after a single intervention [fn 2] and within hours of injection.
6b/ [2] Thompson JF et al. Phase 2 Study of Intralesional PV-10 in Refractory Metastatic Melanoma. Ann Surg Oncol. 2015 Jul;22(7):2135-42. doi.org/10.1245/s10434….
7a/ $PVCT: Release of damage associated molecular pattern molecules (DAMPs) and tumor antigens from injected tumor tissue enhances recruitment of dendritic cells, facilitating priming and activation of a functional T-cell response, including activated CD8+ T-cells, CD4+ T-cells,… twitter.com/i/web/status/1…
7b/ Liu H et al. Intralesional rose bengal in melanoma elicits tumor immunity via activation of dendritic cells by the release of high mobility group box 1. Oncotarget. 2016 Jun 21;7(25):37893-37905. doi.org/10.18632/oncot….
8a/ Combination of $PVCT’s intralesional (IL) PV-10 with systemic anti-PD-1 antibodies in murine models of melanoma has yielded enhanced anti-tumor CD8+ T-cell activity against injected and non-injected tumors [fn 4].
8b/ Liu H et al. T cell mediated immunity after combination therapy with intralesional PV-10 and blockade of the PD-1/PD-L1 pathway in a murine melanoma model. PLoS One. 2018 Apr 25;13(4):e0196033. doi.org/10.1371/journa….
10/ $PVCT’s PV-10 administered in combination with $MRK’s #Keytruda (#pembrolizumab) in patients with advanced cutaneous melanoma is the subject of an ongoing Phase 1b/2 clinical study (NCT02557321), where IL injection facilitates priming and activation of a functional T-cell… twitter.com/i/web/status/1…
10b/ Zager JS et al. Response for combination of PV-10 autolytic immunotherapy and immune checkpoint blockade in stage III cutaneous melanoma. Melanoma Bridge 2022. provectusbio.com/media/docs/Mel…
11/ #InduceAndBoost. * PV-10 induces a precise, personalized immune response that PD-1 boosts *
THREAD END.
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