LAUSR

The field of anti-CD40 agonistic antibody therapies is still awaiting the breakthrough in the clinic. Anti-CD40 agonistic antibodies should in theory complement anti-PD1/PDL1 therapy as they provide the necessary CD40 stimulation to antigen-presenting cells, thereby priming T cells in the presence of tumor antigen presentation in the absence of helper T cells. The preclinical effect has been well documented and there are several models providing evidence of efficacy, mainly driven by CD8 T cell priming and T cell mediated anti-tumor responses. However, as an infusion therapeutic and monotherapy in the clinic, there has so far been limited success and research has shown that we need to rethink the clinical use of anti-CD40 therapies and as such the field is expanding with novel administration routes, combination strategies and multi-specific antibodies to improve therapeutic responses. In addition to their anti-tumor effects via T cells, CD40 agonistic therapies can mediate anti-tumor activity via macrophages along with direct cytotoxic anti-tumor effects on CD40 positive tumors, and can also attract/stimulate myeloid cells. As such the indication of choice, the tumor microenvironment and the route of administration of these antibodies can impact the resulting immune response and should be considered when entering clinical trial evaluation.