Adoptive Cell Therapy NY-ESO-1 TCRT Cells for Metastatic Tumors
Conventional cancer therapies such as chemotherapeutic drugs and radiotherapy typically have low specificity and can act on both healthy and diseased tissues, generating severe side effects. This low specificity laid the ground for the development of targeted-therapy approaches, including various immunotherapeutic modalities. Among the main approaches employed in immunotherapy is adoptive cell transfer (ACT).
ACT has gained recognition as a potential therapy for cancer patients due to its ability to enhance immune system function or improve the effectiveness and longevity of immune cells transferred to the patient. Both preclinical and clinical studies have displayed different levels of feasibility, safety, and efficacy in utilizing TCR-engineered T cells to combat cancer and viral infections. Among various antigens used in immune-based interventions, NY-ESO-1 has emerged as the most promising option. This antigen exhibits a favorable safety profile since it is predominantly expressed on tumor cells rather than healthy tissues, except for the testis. Notably, NY-ESO-1 is highly expressed in challenging-to-treat tumors like synovial sarcoma, triple negative breast cancer (TNBC), uveal melanoma (UM) and others that have limited treatment alternatives.
Nonetheless, despite the advances in the field achieved in the past years, there remains a requirement for the development of TCRs that demonstrate enhanced expression and function, ensuring durable responses.
Prof. Michal Lotem and her team at the Hadassah Cancer Research Institute (HCRI) have successfully developed an optimized version of the NY-ESO-1 TCR called HBI0201-ESO. This new TCR exhibits enhanced stability, affinity, and a unique chain pairing specifically tailored for its target. In pre-clinical proof-of-concept studies, HBI0201-ESO has demonstrated superior activity compared to the previous generation of NY-ESO-1 TCR tested in clinical trials conducted by the NIH. The HBI0201-ESO product comprises of mostly CD8 cells, resulting in increased secretion of cytokines and efficient target killing upon recognition. The composition of the product mainly consists of effector cells, but also a substantial number of central memory cells.
Metastatic solid tumors
In a pre-clinical proof-of-concept study conducted in NSG mice, the HBI0201-ESO T cells demonstrated remarkable tumor elimination and exhibited prolonged persistence. Currently, an ongoing Phase I/IIa Dose Escalation, Safety, and Efficacy Study of HBI0201-ESO TCRT is being conducted as a first-in-human trial for patients with metastatic cancers expressing NY-ESO-1 (NCT05296564). Thus far, six patients with various tumor indications, including synovial sarcoma, UM, TNBC, and ovarian carcinoma, have received treatment. The interim results indicate a positive safety profile, with limited manageable adverse events. Furthermore, there has been a notable extended presence of HBI0201-ESO TCR+ cells following adoptive cell transfer (ACT) for a duration of up to eight months.
The global T-Cell therapy market was valued at USD $2.83 billion in 2022 and is projected to grow at a substantial CAGR of 35.33% until 2030. With numerous cell therapies already approved (e.g., Tecartus®, Yescarta®, and Kymriah®), many biotech companies have shifted their business model from the development of small molecule and protein-based treatments to adoptive therapies.