T-Cells in the Human Immune System, and the Role of Oncolytic Immunotherapy

Cancer immunotherapy activates the immune system to attack cancer. Currently there are several products on the market and many others in the development phase. However, existing drugs typically aim to enhance the pre-existing anti-tumor immune responses (passive immunotherapy) with clinical activity in a limited number of cancer types. Targovax is developing active cancer immunotherapy products that have shown potential to activate the immune system of last-line refractory cancer patients with a wide range of solid tumors.

Figures below present a simplified model of how this adenovirus-based immunotherapy approach induces systemic antitumor T-cell response.

The human innate immune system continuously monitors the body to recognize threats. Dendritic cells (DCs) are the link between the innate and the adaptive immune system. DCs process antigens and provide activating signals to the T-cells in lymphoid organs. As a result, the systemic anti-tumor immune response is achieved by the activated T-cells recognizing cells expressing the antigen.

1. Without treatment

Tumors have many mechanisms to hide from the immune system. Importantly, as most tumor antigens are non-mutated and essentially the same as in normal cells, and therefore hidden from the immune system, a meaningful anti-tumor response is not elicited. Cancers with high mutation rates, such as melanoma and non-small cell lung cancer, are considered immunogenic, since endogenous T-cell responses against tumors often exist.

2. Cancer immunotherapy with current products

Current cancer immunotherapy products can be classified in three main categories:

  1. Oncolytic immunotherapies and innate immune system activators which aim to activate the innate immune system for the induction of subsequent adaptive tumor-specific immune response
  2. Adoptive cell transfer; where patient-derived innate immune cells or T-cells are manipulated ex vivo and returned back into the patient with the goal of transferring a functional antitumor immunity
  3. Agents that aim to potentiate pre-existing anti-tumor T-cell responses.

None of these approaches efficiently modulate the immunological microenvironment at the tumor site which is needed for the induction and maintenance of tumor specific immune response in immune compromised settings.

3. Adenovirus-based oncolytic immunotherapies from Targovax

Targovax’s adenovirus-based technology has been shown to induce a powerful and specific anti-tumor response even in immune compromised patients. Its lead clinical agent, ONCOS-102, administered locally, induces a systemic anti-tumor immune response (“in situ vaccination”) that involves:

  1. activation of the innate immune system
  2. activation of tumor specific T-cells
  3. systemic T-cell mediated immune attack against tumors.