Innovative, safe and highly effective therapeutics that address today’s cancer treatment challenges.
Innovative, safe and highly effective therapeutics that address today’s cancer treatment challenges.
IL-2 Therapies
IL-2 mediates complete and durable regression of metastatic disease in a small percentage of RCC and melanoma patients. However, high doses are required for therapeutic effects which leads to off-target side effects.
Twain Therapeutics was founded using core strategies development by Cheng I Wang and John E Connolly. Years of research at Singapore’s prestigious A*STAR research institutes (Singapore Institute of Immunology and Institute of Molecular and Cellular Biology) and further developments at Tessa Therapeutics resulted in the development of “TRON” a unique agonistic antibody.
This is antibody was designed to bind and activate the IL-2R in a targeted manner which preferentially expands CD8 effector, memory T cells and NK cells whilst avoiding the expansion of regulatory T cells (Tregs) which shut down an effective immune response.
IL-2 Therapies: Interleukin-2 (IL-2) Therapies and Indications
IL-2 induces expansion of T cells and NK cells and promotes a cytotoxic T cell-mediated anti-tumor respons1.0 e.
IL-2 mediates complete and durable regression of metastatic disease in a small percentage of RCC and melanoma patients. Proleukin® was approved for metastatic renal cell carcinoma in 1992 and for metastatic melanoma in 1998.
Limitations and side effects of IL-2 Therapy
IL-2 has a short in vivo half-life of several minutes. This necessitates a high-dose regimen which exacerbates side effects and toxicities. Low-dose regimens reduce toxicities, at the expense of poor therapeutic efficacy.
IL-2 therapy can result in Toxicity and Vascular Leak Syndrome (VLS). This is characterised by hypotension, pulmonary edema, cardiac insufficiency, liver damage and renal failure. It is due to the massive release of pro-inflammatory cytokines from activated immune cells and direct binding of IL-2 to endothelial cells.
IL-2 therapy also results in preferential expansion of regulatory T cells. IL-2 drives the expansion of immunosuppressive T-regs, which leads to dampening of cytotoxic CD8 T cell responses and reduced anti-tumor efficacy.
Twain Therapeutic’s IL2 technology “TRON” is based on a targeted antibody-based IL-2 approach.
Twain’s “TRON” approach both targets stimulation of cytotoxic T cells and NK cells, which can attack cancer cells and also increases the half-life of the therapeutic, which ultimately increases the therapeutic index and reduces the likelihood of side effects. Our TRON molecules are targeted to amplify CD8 & NK cell responses, whilst minimising Tregs & endothelial cell responses.
Our in vitro studies on our candidate molecules showed effective STAT5 signalling in T cells and NK cells. TRON preferentially expanded CD8 T cells with minimal effect on regulatory T cells. TRON additionally inhibits binding of IL-2 to the trimeric IL-2R complex.
A similar expansion of CD8 T cells over Tregs was found in in vivo models. In these systems TRON showed increased efficacy in reducing tumor burdens at metastatic sites compared to IL-2.