Combined Therapy of PD-1 and VISTA

Introduction to Combined Therapy

As critical mechanisms limiting T cell response, the negative checkpoint regulator (NCR) blockade has been served as a cornerstone to multi-modality cancer treatment. In recent years, combination immunotherapy has risen to the forefront of cancer treatment. The investigations about the combined therapy of PD-1 and VISTA have generated promising results in preclinical studies and/or clinical trials.

Research for Combined Therapy of PD-1 and VISTA

V-domain Ig suppressor of T cell activation (VISTA), also known as PD-1 homolog or DD-1α, is a co-inhibitory receptor of the B7 family. It is mainly expressed on hematopoietic cells and myeloid cells in tumors to mediate immune evasion. Besides, VISTA is also expressed on naïve T cells, and its inhibition can promote early T cell reaction in response to tumor cells. According to the interaction with its putative ligand VSIG-3, VISTA may participate in the suppression of T-eff responses and T-reg induction. In the presence of TCR signaling, the VSIG-3/VISTA pathway may impair T cell proliferation and inhibit T cell function.

In the B16-OVA murine melanoma model, the monoclonal antibody 13F3 targeting VISTA enhanced T-eff response within the tumor microenvironment (TME). The blockade of VISTA could enhance innate immunity and thereby promoting early melanoma eradication. The recent studies showed that VISTA could control T cell activation through nonredundant functions distinct from the PD-1/PD-L1 pathway. In this case, the combined therapy of PD-1 and VISTA presents great potentials for cancer treatment. A small-molecule antagonist electively targeting VISTA and PD-L1/2 revealed remarkable anti-tumor effects in a preclinical study. It is presently tested in a phase I trial (NCT02812875) in patients with advanced solid tumors and lymphomas.

Fig.1 VISTA functions non-redundantly to NCRs currently targeted in clinic. (Deng, J 2016)

Services at Creative Biolabs

Creative Biolabs is a leading service provider that focuses on combined therapy against multiple cancers. Based on our advanced drug discovery platform and extensive experience, now Creative Biolabs helps for combined therapy research of PD-1 and VISTA against multiple cancers for our clients all over the world; the services we provide include but not limited to:

• Immune Checkpoint Antibody Development
• Immune Checkpoint Targeted Small Molecule Drug Development
• Immune Checkpoint Assays
• Custom Immune Checkpoint Protein Development
• Immune Checkpoint Targeted Peptide Development
• Preclinical Research for Immune Checkpoint Drugs

If you are interested in our services, please do not hesitate to contact us for more detailed information.

Reference

1. Deng, J.; et al. A New VISTA on combination therapy for negative checkpoint regulator blockade. Journal for immunotherapy of cancer. 2016, 4(1): 1-7.

All listed customized services & products are for research use only, not intended for pharmaceutical, diagnostic, therapeutic, or any in vivo human use.