Tag: Cornelis Melief

Company News: ISA Pharmaceuticals Further Strengthens IP Position on Lead Compound ISA101

Three additional European patents and market exclusivity granted for the use of key active ingredients of ISA101

ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced it has strengthened the IP position of its lead compound ISA101. The European Patent Office has granted three patents (EP2267132, EP2112157, EP2468763) which relate to the use of HPV antigen-based peptides. ISA101, a novel immunotherapeutic consisting of synthetic long peptides (SLP®s), targets severe diseases triggered by human papillomavirus (HPV) infection.

The patents cover the application of a variety of long peptides derived from the E6 and E7 proteins of HPV, including novel epitopes or peptides with specified features, and provide exclusivity for the treatment of persistent HPV infections and resulting diseases.

ISA101 is based on ISA Pharmaceuticals´ proprietary SLP® platform and is currently in clinical Phase I/II trials in cervical cancer and anal intraepithelial neoplasia (AIN).

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.

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* 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

Company News: ISA Pharmaceuticals Granted European Patent for the Intradermal Administration of ISA101

Intradermal administration provides significant benefits compared to subcutaneous application

ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced it has been granted a European patent (patent no. EP 2 155 240) for the intradermal administration of synthetic long peptides (SLP®s) based on HPV oncogenes, including its lead compound ISA101.

Specifically, the patent was granted for the therapeutic use of intradermally delivered long peptides derived from the E2, E6 and/or E7 proteins of the human papillomavirus (HPV) to treat or prevent HPV-related diseases.

ISA101 is a clinical-stage immunotherapeutic for the treatment of early-stage, advanced and recurrent cancers induced by HPV16 infections and is based on ISA Pharmaceuticals´ proprietary SLP® platform. The compound is currently in clinical Phase I/II trials in cervical cancer and anal intraepithelial neoplasia (AIN).

As shown in healthy volunteers, intradermal administration of low doses of the HPV16 E6 and E7 SLP® without any adjuvant resulted in an effective, long-lasting systemic T cell response. This shows that, compared to subcutaneous delivery, the new epidermal routing with lower doses and absence of a concomitant adjuvant is also capable of eliciting a robust immune response in naïve individuals.

 

Company News: ISA Pharmaceuticals Presents Novel Data at the European Cancer Congress 2013 – Strong Synergies Between Cancer Vaccine ISA101 and Chemotherapy

– Chemotherapy improves immune response to therapeutic vaccine against Human Papilloma Virus type 16 (HPV16) –

ISA Pharmaceuticals B.V., a clinical-stage biopharmaceutical company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced that it had presented novel data on its lead compound ISA101 at this year´s European Cancer Congress (ECCO-ESMO-ESTRO) in Amsterdam, The Netherlands.

In a preclinical mouse model of cancer, chemotherapy with cisplatin increased the therapeutic response to subsequent vaccination with an HPV16 synthetic long peptide (SLP®). While cisplatin or HPV-SLP® treatment alone increased survival, long-term survival was only achieved by combining chemotherapy with the vaccine.

These findings are further supported by a Phase I toxicity / immunogenicity study in 18 women with advanced or recurrent cervical cancer eligible for chemotherapy. Concurrent with standard chemotherapy (including carboplatin and paclitaxel), 12 patients received ISA101, a therapeutic cancer vaccine consisting of 13 synthetic long peptides from the E6 and E7 oncoproteins of HPV16. The control group (n=6) did not receive vaccination. The study demonstrates that chemotherapy doe s not cause lymphodepletion or suppression of cellular immune responses in patients. Patients showed shifts in leukocyte composition associated with increased dendritic cell function and improved memory T cell responses to common recall antigens. Patients treated with chemotherapy and ISA101 exhibited robust and sustained HPV16-specific proliferative T cell responses.

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