Tag: Synthetic Long Peptide (SLP®)
Company News: ISA Pharmaceuticals signs R&D agreement with Shin Nippon Biomedical Laboratories
– Experiments to evaluate a novel nasal cervical cancer immunotherapeutic
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, today announced that its fully-owned subsidiary ISA Therapeutics B.V. has closed an R&D agreement with Japan-based Shin Nippon Biomedical Laboratories, Ltd. (SNBL) to explore a novel nasal delivery for ISA’s cervical cancer immunotherapeutic. In the experiments, ISA Pharmaceuticals’ proprietary Synthetic Long Peptide (SLP®) immunotherapeutic ISA101 will be administered via SNBL’s novel nasal drug delivery technology. SNBL´s patent-protected approach is designed to significantly enhance the absorption of powder-based nasal drugs from the nasal mucosa.
Both parties expect to obtain basic research data on a potential antigen-specific immune response.
ISA101 is ISA Pharmaceuticals´ most advanced pipeline program and designed to treat early-stage, advanced and recurrent cancers induced by HPV16 infections. ISA101 is currently administered via subcutaneous injections and has successfully completed several clinical studies in the Netherlands and Belgium for advanced and recurrent cervical cancer, as well as other early-stage HPV16-related cancers.
ISA101 consists of 13 synthetic long peptides (25-35 amino acids long) derived from the E6 and E7 oncogenic proteins of the HPV16 virus. This strain is responsible for 50% of human cervical cancers and cervical intra-epithelial neoplasias and for more than 85% of HPV-positive head and neck cancers, anal cancers and premalignant HPV-induced anal lesions (termed anal intra-epithelial neoplasia, or AIN).
In the United States, cervical cancer is the second most common cancer in women after breast cancer. In Japan, approximately 10,000 women are diagnosed for cervical cancer, and approximately 2,700 infected women die from the disease every year. Since HPV can remain persistent in the body for over a decade before cancer develops, there is a strong demand not only for prophylactic vaccines preventing HPV infections, but also for novel immunotherapeutics to treat already infected individuals.
Company News: ISA Pharmaceuticals – New Study Explains Synergy between Cancer Vaccine ISA101 and Chemotherapy
– Tumor necrosis factor alpha (TNFα) produced by T cells following vaccination sensitizes tumor cells for eradication by certain chemotherapeutics
– Data published in Clinical Cancer Research support ongoing clinical development of ISA101
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed immunotherapeutics against cancer and persistent viral infections, has announced new findings on the synergy between its synthetic long peptide (SLP®) cancer vaccine and chemotherapeutics. Data published in Clinical Cancer Research* demonstrate that combined chemo-immunotherapy leads to superior T cell-mediated tumor eradication in the absence of T cell immunosuppression.
In a preclinical model of cancer induced by human papillomavirus type 16 (HPV16), ISA’s lead SLP® candidate ISA101 was combined with seven clinically relevant chemotherapeutics to treat established tumors. The researchers tested either ISA101 or chemotherapeutics alone as well as combinations of both. Topotecan, gemcitabine, carboplatin and cisplatin showed synergies with ISA101. The most effective combination was cisplatin plus ISA101, resulting in tumor regression and the durable survival of 75% of the mice, and a lasting immune response. Most importantly, synergy occurred to the same extent at only 40% of the maximum tolerated dose (MTD) of cisplatin, allowing for a reduction of chemotherapy-associated side effects as seen at MTD. There was no synergy between ISA101 and oxaliplatin, doxorubicin or paclitaxel.
While synergy was not related to overt changes in systemic T cell immunity or increased sensitivity of cisplatin-treated TC-1 tumor cells towards CTL-mediated killing, there was a strongly enhanced leukocyte infiltration of the tumor. Vaccine-specific polyfunctional CD8 T cells were a major component of this infiltration. The cisplatin allowed these cells to migrate earlier into the tumor beds, enabling them to eliminate tumor cells at an earlier stage of disease. Once inside the tumor, the T cells further enhanced tumor cell death by producing pro-inflammatory cytokines such as IFNγ and TNFα. In particular, TNFα produced by intratumoral T cells sensitized the tumor cells for cisplatin, allowing for synergistic cell death.
Another study presented at AACR in 2014, showed that cis-/carboplatin/paclitaxel depletes myeloid derived suppressor cells in patients, and thereby strongly increases an ISA101-mediated immune response.
This finding supports the ongoing clinical development program in which ISA101 is tested in a Phase I/II study (CervISA) in combination with cisplatin/carboplatin and paclitaxel in women with advanced or recurrent cervical cancer.
* van der Sluis TC et al.: Vaccine-induced Tumor Necrosis Factor producing T-cells synergize with cisplatin to promote tumor cell death. Clin Cancer Res. 2014 Dec. 12 pii: clincanres.2142.2014; Epub 2014 Dec. 12,; doi: 10.1158/1078-0432.CCR-14-2142
Company News: ISA Pharmaceuticals Strengthens Patent Protection for its Lead Product ISA101
– Granted EU patent provides market exclusivity until 2028 –
ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced it has been granted a European patent on its lead compound ISA101. The patent ensures market protection of ISA101’s active ingredient in Europe until 2028.
ISA101 is a therapeutic vaccine for the treatment of high-risk, HPV16-induced diseases. The vaccine consists of synthetic long peptides derived from the E6 and E7 oncogenic proteins of the HPV16 virus. This HPV strain is responsible, among others, for over 50% of human cervical cancers, more than 85% of HPV-positive head and neck cancers, and a variety of premalignant disorders.
The patent covers long peptides of the HPV-E6 protein, including a novel CD4+ epitope and provides exclusivity for the treatment of HPV-related diseases.
ISA101 is currently studied in the CervISA trial, a company-sponsored Phase I/II trial in cervical cancer and anal intra-epithelial neoplasia (AIN). Moreover, the vaccine has established clinical proof-of-concept by successfully completing a Phase II trial in vulvar intraepithelial neoplasia (VIN).
Company News: ISA Pharmaceuticals Initiates Phase I/II Clinical Trial With ISA101 in Women with Cervical Cancer
– Therapeutic vaccine against Human Papilloma Virus type 16 (HPV16) tested together with chemotherapy in women with HPV16-positive advanced or recurrent cervical cancer –
ISA Pharmaceuticals B.V., a clinical-stage biopharmaceutical company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced the initiation of a Phase I/II clinical study of its lead candidate ISA101 in women with HPV16-positive advanced or recurrent cervical cancer, eligible for standard chemotherapy with carboplatin and paclitaxel (CervISA study). The first patient was vaccinated this month.
ISA101 is a synthetic long peptide (SLP®) vaccine for the treatment of diseases induced by human papilloma virus (HPV) type 16, such as cervical cancer, ano-genital premalignant and malignant lesions, and head and neck cancer.
The open-label, multicenter CervISA study is designed to determine the safety and immune-modulating effects of ISA101 at different doses with or without pegylated interferon alpha in combination with carboplatin and paclitaxel.
Patients will receive up to six standard chemotherapy cycles (paclitaxel 175 mg/m2 and carboplatin AUC 6 every three weeks) and three vaccinations at different dose levels during the same period. Half the women at each dose level will also receive pegylated interferon alpha. Primary endpoints of the trial are safety and HPV-specific immune responses. The secondary endpoint is antitumor efficacy according to RECIST 1.1.
Virtually all cervical cancers are caused by HPV infections, with HPV16 being responsible for about 50-60% percent of all cases.