T-ALL comprises 10–15% of all acute leukemias diagnosed in children and 20–25% in adults, with a median diagnostic age of 9 years. Survival of patients with T-ALL treated with intensive chemotherapy remains less than 70%, and relapsed/refractory (r/r) T-ALL has a particularly poor outcome of 6% to 20% in 5 to 10 years. OC-1 is a CART CD1a Immunotherapy developed as a treatment for refractory relapsed patients with cortical T-ALL, a T-ALL subgroup without many options to date. OC-1 received Orphan Drug Designation (ODD) from the EMA in 2021.
OC-1 covers the co-T-ALL subtype which represents 30-40% of all T-ALL. In this sense, OneChain has identified OC-1.2 as a new target for T-ALL patients, and humanized OC-1.2-directed CARs have been developed, encouraging the development of a dual CD1a/OC-1.2 CAR (OC-1d). Dual targeting of these T-ALL-specific antigens will: i) widen the number of R/R T-ALL patients eligible for CART therapy; and ii) reduce the likelihood of immune escape due to the distribution of the immune pressure between the two antigens. We calculate that this OC-1d will extensively widen the inclusion criteria to approx. 80% of all R/R T-ALL patients, representing a unique advancement in the treatment of such an orphan and unmet clinical need.
B-ALL is the most common cancer in children and despite current 5-year disease-free survival rates of 80%, relapsed/refractory (r/r) patients still have a dismal outcome. B-ALL is less frequent in adults and still associated with unfavorable clinical outcomes. OC-2 immunotherapy, based on a bispecific CART, is an alternative treatment to salvage chemotherapy followed by autologous stem cell transplantation only suitable for 50% of eligible patients with r/r B-ALL.
Recently, γδ T cells have emerged as an alternative to αβ T cells for cellular immunotherapy. They are not constrained by MHC presentation of tumor‐associated peptides but, providing robust and durable antitumor responses. OneChain platform is a novel and efficient method for a selective, large‐scale generation of human cytotoxic Vδ1+ γδ T cells. They are very attractive candidates for adoptive cell therapy of cancer. Vδ1 naïve cells are produced in a TCR-independent manner and expanded to induce Vδ1+ T cell proliferation, which allows for a significant-fold expansion.
Glioblastoma multiforme (GBM) is the most common and most aggressive primary brain tumor in humans, presenting an annual incidence of 3.2 cases per 100,000 individuals (U.S). Patients with GBM have a poor prognosis due to the current limited therapeutic approach, resulting in 5-year survival rates between 6% and 27% (2001-2015). OC-4 is a new immunotherapy against GBM, consisting of a dual CAR-T cell strategy targeting IL13a2/OC-4.2-expressing GBM tumor cells and a key component of the immunosuppressive tumor microenvironment.