Photoimmunotherapy: A Targeted Immunotherapy Method in Cancer

Standard cancer treatments include surgery, radiotherapy and chemotherapy. Increasing numbers and varieties of approaches are developed to treat or prevent cancer. Discovering biological features present in cancer but absent in normal cells opened the door to targeted treatments, while better understanding immunity enabled immunotherapies. A newer approach combines them. One excellent example is photoimmunotherapy.

Photoimmunotherapy uses infrared light to rapidly destroy only cancer cells without harming healthy cells.

Cancer cells carry specific surface receptors, or certain receptors are much more abundant than on normal cells. Identifying cancer-specific receptors is very important for developing targeted cancer treatments.

Researchers developed light-absorbing molecules attached to monoclonal antibodies recognizing cancer-specific receptors. When they bind the target receptor, the light-absorbing molecule at the end becomes active. The process is detailed below:

• Patients receive injected monoclonal antibodies recognizing cancer-cell receptors and carrying a light-sensitive molecule.
• The injected antibodies recognize and bind cancer-cell surface receptors, activating the light-sensitive molecule.
• When laser light is applied, the activated molecule disrupts cancer-cell membranes and causes necrosis , a form of cell death. Cellular material, including proteins from dying cells, spreads into the tumor microenvironment. Immune cells recognize these as “foreign” and attack, creating systemic anticancer immunity.

Recent Developments in Photoimmunotherapy

• Research presented in April 2016 at the American Association for Cancer Research Annual Meeting increased antitumor immunity in mouse models using infrared photoimmunotherapy. It targeted immune cells in the tumor microenvironment that prevent antitumor responses.
• In March 2016, Oncotarget published research accurately targeting cancer cells with photoimmunotherapy in cell cultures and mouse models. A light-absorbing monoclonal antibody was developed against the cell-surface protein mesothelin , highly active in mesothelioma, pancreatic and ovarian cancer cells. Cancer cells were destroyed rapidly and selectively without harming normal tissues.
• In November 2016, phase 1 trials began, involving recurrent head and neck cancer patients positive for EGFR1.

How Does Photoimmunotherapy Differ from Other Photodynamic Treatments?

• Photodynamic treatments have two stages. First, photosensitizer molecules designed to accumulate near cancer tissue are injected. Light of a specific wavelength is then delivered. Absorbing molecules generate oxygen radicals, killing nearby cells. Although effective, selectivity is low: normal cells are damaged too, causing serious adverse effects.
• Photoimmunotherapy uses monoclonal antibodies to select cancer cells more specifically and accurately, minimizing damage to normal cells.

Photoimmunotherapy remains experimental. Infrared light cannot be applied to every body region, and lasers do not penetrate deeply. Moreover, tumors in test mice were implanted beneath the skin, and these mice have suppressed immunity, failing to reflect the true human tumor microenvironment. Human trial results are needed to establish efficacy.

Although completely curing most cancers currently seems impossible, we hope within a few decades to make cancer a manageable chronic disease.

References:

1. Sato K. et al., Cancer Treatment by near infrared photoimmunotherapy targeting intratumoral regulatory T cells, Proceedings of the 107th Annual Meeting of American Association for Cancer Research, 2016 April 16-20.
2. Nagaya, T., Nakamura, Y., Sato, K., Zhang, Y., Ni, M., Choyke, P., Ho, M., & Kobayashi, H. (2016). Near infrared photoimmunotherapy with an anti-mesothelin antibody. Oncotarget., 7(17), 23361-23369.
3. Clinical trial Identifier: NCT02422979,A Phase I Multicenter, Open-Label, Dose-Escalation, Combination Study of RM-1929 and Photoimmunotherapy in Patients With Recurrent Head and Neck Cancer, Who in the Opinion of Their Physician, Cannot Be Satisfactorily Treated With Surgery, Radiation or Platinum Chemotherapy