Company News: New Peer-Reviewed Publication Provides Further Insights into Mechanism of ISA Pharmaceuticals’ SLP® Immunotherapeutics

SLP®s modulate intratumoral macrophages required for tumor regression

ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced the publication of a new peer-reviewed paper* demonstrating a beneficial effect of Synthetic Long Peptide (SLP®s) immunotherapeutics on intratumoral macrophages in cancers induced by human papilloma virus 16 (HPV16). ISA’s proprietary SLP® immunotherapeutics are rationally designed, off-the-shelf, synthetic peptides which ISA is developing as cancer immunotherapeutics. The company’s SLP® lead compound ISA101 is in clinical development for the treatment of early-stage, advanced and recurrent cancers induced by HPV16 infections.

Macrophages, a type of white blood cell, play a critical role in immunity by recruiting other immune cells and exerting effector functions, such as phagocytosis and cell or bacterial killing. They exist in two major and opposing types: The so-called M1 macrophages inhibit cell proliferation and cause tissue damage, while M2 macrophages promote cell proliferation and tissue repair. Cancer is often characterized by M2 activity, which facilitates tumor growth via angiogenesis, metastasis formation and suppression of Th1-type immune responses, among others. As a result, M2 macrophage infiltration of tumors commonly correlates with poor prognosis.

Based on these observations, the targeting of macrophages or inhibition of macrophage infiltration is considered a promising therapeutic option in cancer therapy. However, as part of an ongoing investigation into tumor immunotherapy, the authors of the paper cited below were able to demonstrate that skewing the macrophages towards M1 antitumor activity might be the optimal strategy instead. In animal studies, this skewing can be accomplished with ISA’s Synthetic Long Peptide (SLP®) immunotherapeutics.

The team of researchers used a mouse tumor model of HPV-induced cancers, such as cervical cancer, and HPV-positive head and neck cancer. Administration of an SLP® compound, among others, resulted in an influx of cytokine-producing CD8 T cells that strongly altered the numbers and phenotype of intratumoral macrophages from M2 to M1 activity. It was also demonstrated that complete regressions of large established tumors are dependent on the tumor-infiltrating macrophages induced by this immunotherapy: when a small molecule drug inhibitor diminished the number of intratumoral macrophages after SLP® administration, the complete remissions were abrogated and survival rates deteriorated.


* van der Sluis TC et al. (2015), Therapeutic peptide vaccine-induced CD8 T cells strongly modulate intratumoral macrophages required for tumor regression. Cancer Immunol Res. 2015 Apr 17. pii: canimm.0052.2015