Research conducted by ISA Pharmaceuticals B.V. revealed a beneficial effect of Synthetic Long Peptide (SLP®) on intratumoral macrophages in cancer induced by human papilloma virus 16 (HPV16). The study entitled “Therapeutic peptide vaccine-induced CD8 T cells strongly modulate intratumoral macrophages required for tumor regression” was published in Cancer Immunology Research by Leiden University Medical Center researchers.
Macrophages are a type of white blood cell that have a critical role in immunity by recruiting other immune cells and exerting effector functions, such as phagocytosis and cell or bacterial killing. Macrophages have a remarkable plasticity and can change their physiology in response to environmental signals. These changes can give rise to different populations of cells with distinctive functions. There are two main types of macrophages: the M1 macrophages that are produced during cell-mediated immune responses with increased microbicidal or tumoricidal capacity; and the M2 macrophages, which favor wound-healing processes and cell proliferation.
Cancer is normally characterized by M2 activity that promotes tumor growth through angiogenesis, metastasis formation and suppression of Th1-type immune responses. As a result, M2 macrophage infiltration of tumors has been associated with poor prognosis. These observations suggested that targeting macrophages or inhibiting of macrophage infiltration could be a potential therapeutic alternative in cancer treatment.
The research team used a mouse model of HPV-induced tumors treated with an SLP® compound and observed tumor infiltration with cytokine-producing CD8 T cells, that significantly altered the numbers and phenotype of macrophages from M2 to M1 activity. Importantly, the researchers showed that upon inhibition of tumor-infiltrating macrophages induced by SLP, complete tumor remissions were abrogated and survival rates decreased.
Kees Melief, CSO of ISA Therapeutics and co-author of the study, mentioned in a news release that the treatment with SLP immunotherapeutics can induce T cells to produce cytokines with the potential to change macrophage functions towards tumor shrinkage type. He added these results suggest that macrophage-polarizing approaches are the way to follow in tumor therapy rather than macrophage-depleting strategies.
Ronald Loggers, CEO of ISA, explained this skewing into an M1 phenotype can be accomplished with ISA’s SLP® immunotherapeutics. He added that researchers had already observed similar findings in a clinical study with cervical cancer patients, with these recent results reinforcing SLP’s therapeutic potential.