Presentation Title: Intralesional injection with PV-10 induces a systemic anti-tumor immune response in murine models of breast cancer and melanoma
Abstract Body: PV-10 is a 10% solution of Rose Bengal that is currently being examined as a novel cancer therapeutic. In melanoma patients, intralesional injection (IL) of PV-10 has led to regression of injected lesions as well as distant metastases.
Injecting PV-10 into cancers makes them go away (Provectus' clinical trials and studies in mice and its previous studies). Also, PV-10 makes untreated remote tumors go away (bystander effect as Provectus has called it).
In this study, we examined the efficacy and potential immune mechanism of PV-10 treatment in murine models of breast cancer and melanoma.
Moffitt studied how well PV-10 works (efficacy) in multiple types of tumors. Confirms Provectus' previous observations and conclusions that PV-10 works on more than just melanoma.
In BALB/c mice bearing MT-901 breast cancer, injection of PV-10 led to regression of injected and untreated contralateral subcutaneous lesions (p<0.05 compared to IL-PBS-treated mice).
PV-10 causes breast cancers to regress and control injections of salt water (in what PV-10 is dissolved) did not. PV-10 is doing it, and not the injection or salt water. This shows PV-10 works on breast cancer and demonstrates the bystander effect on breast tumors. Confirms what Provectus has claimed that PV-10 works on multiple tumor types.
A significant increase in survival was observed in mice treated with PV-10.
This is the hallmark of cancer treatment. The FDA only recognizes increases in life span. Treated mice with PV-10 live longer.
To examine immune response, MT901-specific IFN-gamma production and cytotoxicity were measured in splenocytes collected from mice treated with IL-PBS or IL-PV-10. MT901-bearing mice treated with IL-PV-10 demonstrated enhanced IFN-gamma production (992 ± 453 pg/ml) compared to splenocytes from PBS-treated mice (174 ± 105, p<0.05).
Moffitt took spleen cells from mice who were treated with tumors on the skin. Tumors were treated with PV-10 or an injection control (the solvent, which is salt water, alone). The immune cells from the spleen are making a large amount of a chemical made by immune cells (gamma interferon) compared to ones with salt water. PV-10 is activating the cells. Shows specific system wide activation, and not some generic irritation of the immune system. Confirms the same claim by Provectus using a different method in live animals.
In addition, a significant increase in lysis of MT-901 cells by T cells after PV-10 treatment was observed (p<0.01 compared to PBS-treated mice). No lysis of irrelevant CT-26 cells was detected.
Moffitt took T cells and showed they could kill cancer cells and it was very, very specific to the type of cancer that had been treated with PV-10. Demonstrates T cells are involved. Killing is very specific. Confirms Provectus' claims in studies in mice with no T cells that T cells are part of the killing of the cancer and it's very specific.
In a murine model of melanoma, B16-F10 cells were injected into C57BL/6 mice to establish one subcutaneous tumor and multiple lung lesions. Treatment of the subcutaneous lesion with a single injection of IL-PV-10 led to regression of the injected lesion as well as distant B16 melanoma lung metastases.
Moffitt treated mice with a melanoma in their flank using PV-10. Treated tumors go away, as do remote tumors in lungs. Tumors in lungs go away (bystander effect). This is an extremely harsh model. Nobody has ever seen anything like this before. Provectus can confirm and repeat Moffitt's results.
In B16-bearing mice, treatment with IL-PV-10 led to the induction of T cells that produced IFN-gamma in response to B16 tumors but not irrelevant tumor (p<0.05) and demonstrated specific lysis of B16 (p<0.01 compared to T cells isolated from PBS-treated mice).
Same interferon induction if the tumor is melanoma or breast cancer. PV-10's very specific anti-tumor immunity is creating the bystander effect. Works on multiple cancers, as Provectus previously has claimed. Also, T cells can lyse (explode) melanoma cells. This “killing” activity has been induced remote from the treated tumor. It's why the bystander effect works.
In total, these studies support the induction of tumor-specific T cell-mediated immunity after single treatment with IL-PV-10 in multiple histologic subtypes. The immune mechanism of PV-10 ablation in cutaneous melanoma patients is currently under investigation at our institution.
Using PV-10 injected into a tumor makes the mice produce immunity with different cancers, it's very specific, and T cells are involved in doing it.
- Everything Provectus previously claimed has been confirmed using similar studies and different experimental designs.
- Conclusions advanced by Provectus previously are confirmed, even in harsher models. T cells are involved. Induction of system wide immunity. PV-10 works on multiple types of cancer.
- Provectus can confirm the results from Moffitt's mouse lung metastasis model.
A small molecule drug delivered directly into tumors kills them, and induces remote immunity that kills remote metastases in an incredible harsh model.