Peptides For Solid Cancer Tumor Immunotherapy Treatment

Short, multivalent peptide antagonists to block macrophage immune-receptor SIRPα, promoting cancer cell phagocytosis.
Problem:
Modern cancer cell immunotherapies incorporate immune checkpoint blockade mechanisms, where prominent therapies target functionally suppressed immune cells in tumor microenvironments. Relieving this suppression allows immune cell simulation, eliminating targets of cancer. Current strategies for immune checkpoint blockades focus on T cells, which can be stimulated through immunotherapy to destroy cancer cells. This treatment is ineffective on solid tumors, as T cells cannot infiltrate into solid tumors. Additionally, indiscriminate immune checkpoint blockading of healthy cells such as blood cells can lead to toxic side effects, such as anemia.
Solution:
A macrophage-based treatment which can infiltrate into solid tumors, allowing for the treatment of both liquid- and solid-state tumors. This treatment targets a less-abundant immune receptor compared to existing immunotherapy techniques, resulting in potentially reduced side effects.
Technology:
Macrophages have innate immune responses to solid tumors and are able to clear foreign cells through phagocytosis. All healthy cells, as well as cancer cells, express the CD47 protein, which signals to macrophages through the immune receptor SIRPα, that the cell should not be destroyed. By designing multivalent peptides to bind and block SIRPα, macrophages perform phagocytosis on the target cells, as they are no longer identified as “self.” By targeting SIRPα, which is expressed only on macrophages, rather than CD47, which is ubiquitous throughout the body, destruction of healthy cells can be minimized, reducing the probability of side effects.
Advantages:

Macrophage-based mechanism allows for treatment of solid tumors
Targeting of SIRPα rather than CD47 reduces side effects such as anemia
Synthesized peptides outcompete soluble CD47 binding to macrophages, consistent with effective SIRPα binding
Use of multivalent peptides is comparatively more potent compared to existing monovalent 8-mers as agonists for phagocytosis of target cells

Stage of Development:

Proof of Concept
Bench Prototype

CD47 binding to SIRPα signals “don’t eat me” to the macrophage (leftmost). Antibody blockade of CD47 OR antibody opsonization alone does not enable efficient target engulfment (middle two). Blockade of CD47 signaling on the macrophage (anti-SIRPα) or the cancer cell (anti-CD47) combined with antibody opsonization enables efficient phagocytosis (rightmost).