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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: After U.S. court ruling, Merus reaffirms freedom to operate for its MeMo® transgenic mouse for therapeutic human antibodies
– Regeneron’s ‘018 patent’ is considered invalid and Merus not infringing –
Merus B.V., a leader in developing best-in-class antibody therapeutics to treat cancer patients, today announced a series of pivotal events in its litigation with Regeneron Pharmaceuticals Inc. Previously, Regeneron sued Merus accusing it of infringing U.S. Patent No. 8,502,018 (‘018 patent’) directed to a particular method of making a genetically modified mouse, which Regeneron asserted was useful to produce therapeutic antibodies.
Merus argued that Regeneron had interpreted its patent in an overbroad manner, and that the patent claims were indefinite and invalid. On November 21, 2014, in a fifty-nine page decision, the United States District Court for the Southern District of New York agreed with Merus on virtually every issue, stating: “[t]his Court generally agrees with the constructions Merus proposes, limiting the Patent to a far narrower scope than asserted by Regeneron.” The court also ruled that Merus has demonstrated “clear and convincing evidence that [a key claim term] lacks reasonable certainty and is therefore indefinite.” On December 19, 2014, Regeneron filed papers with the court conceding that under these rulings, Merus does not infringe any asserted claim of the ‘018 patent, and that these claims are invalid. With this ruling and Regeneron’ s concessions, there are no outstanding claims against Merus. The only remaining issues include Merus’ claim against Regeneron that it unlawfully procured its patent from the U.S. Patent Office and Merus’ request that Regeneron pay the legal fees incurred by Merus.
Company News: Anergis Granted U.S. Patent for Ragweed Allergy Vaccine AllerR
– Anergis receives notice of allowance from U.S. Patent Office for patent on ultra-fast treatment for ragweed allergies
Anergis, a company developing proprietary ultra-fast allergy vaccines, today announced that it received a notice of allowance from the U.S. patent authorities for its patent covering composition and methods of use of its ragweed allergy product AllerR. AllerR is based on Anergis´ unique Contiguous Overlapping Peptide (COP) platform. COPs are pharmaceutical-grade, long-peptide immunotherapeutics designed for an ultra-fast, safe and long-lasting treatment of allergy patients.
Ragweed pollen is believed to be the most allergenic of all pollens. Allergies to ragweed pollen are mostly prevalent in the USA, where they affect an estimated 27 million patients, with a high degree of severity in many of them. Among others, ragweed allergies are a major cause of asthma. Fifty percent (50%) of allergic patients in the United States are sensitized to ragweed.