TIL Technology

About TIL

In the early stages of cancer, the immune system tries to fight cancer by mobilizing special immune cells known as lymphocytes to attack the tumor. Lymphocytes with the capacity to recognize and attack the tumor traffic to, and infiltrate into the tumor. These cells are known as tumor infiltrating lymphocytes (TIL). However, the anti-tumor effect of the TIL is usually short-lived because cancer cells adapt and employ mechanisms to evade detection by TIL, and suppress the anti-tumor immune response through the release of various anti-inflammatory factors into the local environment.

Iovance’s TIL technology is designed to address the manifold obstacles that attenuate the natural anti-tumor immune response. First, TIL are extracted from the patient and expanded to billions in number by stimulating them ex vivo (in tissue culture) with IL-2. Second, the amplification process eliminates the immune-suppressive environment created by the tumor which is so effective at neutralizing the natural anti-tumor immune response. Third, this same culture environment optimizes the replication and activation of aggressive anti-tumor TIL. Once sufficient numbers of cells with the appropriate anti-tumor potential have been cultured, they are then re-administered back into the donor patient where they have been shown to mediate impressive anti-tumor responses.

In Phase-2 clinical studies in patients with metastatic melanoma performed by Steven A. Rosenberg, MD, chief of surgery at the National Cancer Institute (NCI), TIL therapy demonstrated robust efficacy in patients with metastatic melanoma with objective response rates of 56% and complete response rates of 24%.

Problem

Cancer suppresses and evades immune system

Tumor heterogeneity Cancer consists of many different cell types that can mutate hundreds of times over, allowing them to evade immune detection.

Insufficient T-cell response Tumor micro-environment deactivates T-cells and inhibits their growth, so they are insufficient in number and potency to mount an adequate immune response.

Immune suppression Proteins on the surface of tumor cells, such as PD-1 and CTLA4, inhibit T-cell response.

Our Solution: TIL Technology

Enables and enhances robust immune response

Targeting patient-specific antigens Unlike many cancer vaccines which target pre-selected tumor antigens, our technology is based on a patient’s own TIL, which naturally target antigens specific to that patient’s tumor.

Enhancing T-cell number and potency TIL isolated from a resected tumor are expanded to several billion cells ex vivo, away from suppressive influences, enabling administration of potent, highly activated cells.

Controlling tumor micro-environment to reduce immune suppression Patient is preconditioned to remove all suppressive influences prior to infusion of cultured TIL to enhance therapeutic outcome.