PHOTOIMMUNTHERAPY: A NEW PRECISION TARGETED APPROACH TO TREAT CANCER
Photoimmunotherapy (PIT) is a new tumor-targeted anticancer platform that can induce a rapid and specific destruction of the tumor. PIT is unique in that it combines molecular targeting of the cancer cells to achieve high tumor specificity, together with a biophysical mechanism of cancer cell destruction that results in broad spectrum anticancer activity regardless of the tumorigenic mechanism of the patients’ tumor. PIT was originally invented at the National Cancer Institute and licensed under exclusivity by Rakuten Medical.
PIT treatments consist of a drug (a cancer-targeting photoactivatable antibody conjugate) and a device system to apply light at the tumor site. The light application system includes a laser device and light diffusers to enable the illumination of the tumor using normal red-light energy below the thermal threshold. The red light activates and triggers the drug’s pharmacological activity, resulting in acute tumor necrosis.
In the clinical setting, the drug (antibody conjugate) is provided as a parenteral solution, ready for infusion. The drug is administered intravenously and allowed to distribute systemically for about one day. During this period, the drug will accumulate in the tumor and will bind to cancer antigens expressed by the cancer cells. Unless activated with red light, the drug does not have anticancer activity in either the tumor or normal tissues.
One day post-infusion, the light diffusers are placed at or into the tumor using standard techniques including ultra-sound or computed tomography (CT)-guidance. Superficial tumors can be treated with frontal diffusers, while multiple cylindrical diffusers can be implanted into subcutaneous tumors to treat large tumor volumes. Local illumination of the tumor with red light for approximately 5 minutes is sufficient to activate the anticancer activity of the drug resulting in cancer cell membrane destruction and tumor necrosis.
Yes. Tumor destruction with Photoimmunotherapy causes rapid necrosis (cell death), immunogenic cell death, acute inflammation, activation of innate immunity (antigen presenting cells and NK cells) and activation of adaptive immune responses (cytotoxic T-cell activation). In preclinical cancer mouse models, PIT induced destruction of the cancer cells elicits robust immunological responses that are synergistic with other types of immunomodulators such as anti-PD1 therapy. Combination treatments result in rapid activation of tumor specific anticancer immune responses with long-term memory resulting in vaccination of the animals to the cancer. In patients, evidence of immune activation due to Photoimmunotherapy treatments has been detected using a range of correlative studies that measured phenotypic activation of the innate and adaptive immune system and inflammatory biomarkers. Given the strong immune responses activated by Photoimmunotherapy, Rakuten Medical plans to initiate Phase 2 studies of ASP-1929 in combination with immunomodulatory agents in the second half of 2018.
Photoimmunotherapy drugs are conjugates of monoclocal antibodies with a photoactivatable payload and are designed to target antigens expressed at cancer cells. The antibody provides highly effective and specific cancer targeting. In addition, light activation of the antibody conjugate at the tumor site enables the destruction of cells that are bound to the antibody conjugate while sparing damage to normal organs.
Photoimmunotherapy antibody conjugates can be designed to target a broad range of antigens and solid tumors with precision and cancer specificity. Rakuten Medical’s first investigational medical product based on the Photoimmunotherapy platform, ASP-1929, is designed to target EGFR antigens, that could be used to treat squamous cell carcinomas of the head and neck, skin, and other cancers including bladder cancer, esophageal cancer, glioblastoma multiforme, etc.
The method of action described herein relates to a treatment platform currently under development by Rakuten Medical. This treatment has not been approved by the FDA.
Because of its distinctive features, Photoimmunotherapy combines molecular mechanisms and biophysics to achieve a new mode of cancer killing that is rapid and specific and can both destroy the tumor while activating anticancer immune responses. Hence, Photoimmunotherapy presents a new anticancer platform that can be used as a monotherapy but can also complement and synergize other anticancer treatments such as systemic agents and immunomodulators.
The immune system is naturally responsible for eliminating cancer cells, but tumors adopt multiple strategies to silence and inhibit the immune system from attacking the cancer. Tumor killing by photoimmunotherapy serves as an ignition mechanism to reinvigorate the activity of the immune system so it can overcome inhibitory mechanisms used by the tumors. Combinations of PIT treatments with immunomodulators are expected to provide synergistic anticancer activity and possibly generating long-term immunological memory for in vivo vaccinations of the patient to its own personal tumor.
