Adaptimmune Therapeutics has started the first clinical trial (SURPASS) of its next-generation SPEAR T-cell, ADP‑A2M4CD8, for the treatment of solid tumours.
The company’s SPEAR T-cell platform allows the identification of targets, selection and engineering of T-cell receptors to targets, and preclinical screening of end T-cell therapies.
ADP‑A2M4CD8 expresses the CD8α co-receptor and the engineered TCR, which targets MAGE-A4.
In preclinical studies, co-expression of CD8α demonstrated the potential for an increased immune response against solid tumours.
It may also lead to enhanced anti-tumour activity by leveraging CD4+ cells into CD8+ killer or cytotoxic T‑cells while retaining CD4+ helper function.
Adaptimmune Therapeutics Research and Development president Rafael Amado said: “We are delighted to have started screening for the SURPASS study, not only because it is our first next‑generation SPEAR T-cell to be evaluated as an improvement to affinity matured TCRs in a clinical trial, but also because it is the first of three studies we plan to start in the second half of this year to assess the safety and efficacy of our SPEAR T-cell platform.
“The preclinical data we presented at AACR indicate that adding CD8α may enhance the ability of CD4+ SPEAR T-cells to kill tumour cells and broaden antigen presentation.”
The new SURPASS study will assess ADP‑A2M4CD8 in a total of up to 30 patients with various solid tumours.
The dose-escalation study will include three subjects in three dose cohorts, which can be expanded to six patients if dose-limiting toxicity occurs.
SURPASS will involve a starting dose of 800 million to 1.2 billion SPEAR T‑cells in the first cohort. The remaining two cohorts will see dose ranges of 1.2 billion to three billion and three to six billion SPEAR T-cells, respectively.
The dose-escalation phase will be followed by an expansion phase involving doses of up to ten billion cells.