5T4 is a tumour antigen found in a variety of malignancies including non-small cell lung, renal, pancreas, prostate, breast, colorectal, gastric, ovarian and cervical cancers. As it has a limited expression on healthy tissue, it is an attractive target for cancer immunotherapy.
ALG.APV-527 is a bispecific antibody created using Aptevo’s ADAPTIR platform and binding domains sourced from Alligator’s human scFV library. It is formed of two parts; one that activates tumour-specific T-cells through the co-stimulatory receptor 4-1BB, and the second, which binds to the 5T4 protein on the surface of tumour cells. As such, it simultaneously targets 5T4 and the co-stimulatory receptor 4-1BB (CD137) to stimulate tumour-directed immune T-cell activation. This structure allows the antibody’s immune-activating effect to be directed specifically at the tumour and not healthy tissue.
Preclinical data has demonstrated ALG.APV-527’s ability to selectively stimulate and improve tumour-specific T-cell responses at the tumour site without causing systemic immune activation. The companies involved have expressed their belief that by specifically targeting 4-1BB within the tumour microenvironment, restrictions seen with other 4-1BB therapies could be avoided.
Findings were presented at the recent PEGS Summit and AMERICAN ASSOCIATION OF IMMUNOLOGISTS (AAI ) annual meeting, and are due to be presented next week at the annual meeting of the Association for Cancer Immunotherapy (CIMT).
“Taken together, the accumulating preclinical data package for ALG.APV-527 support its potential to provide effective tumour-directed immune activation with reduced systemic side effects,” Alligator vice president Christina Furebring said.
“We are continuing to advance this candidate and look forward to commencing clinical development in 2019.”
Aptevo chief science officer Jane Gross said:“Our collaboration with Alligator Bioscience continues to yield encouraging data supporting the advantages of this novel pathway for targeted immunotherapy of cancer.
“As a first-in-class molecule, ALG.APV-527 showcases the versatility of our ADAPTIR platform in generating bispecific antibodies with unique mechanisms of action and a therapeutic profile that is more consistent with traditional antibodies, including an extended half-life, desirable antibody-like manufacturing characteristics and increased potency and stability.”
Aptevo is a biotech that works to develop immuno-oncology and haematology therapeutics, while Alligator Bioscience develops antibody-based medications for tumour-directed immunotherapies. Alligator’s pipeline includes four lead clinical and pre-clinical drug candidates: ADC-1013, ATOR-1015, ATOR-1017 and ALG.APV-527.