Tag: melanoma

Company News: Three Peer-Reviewed Papers by ISA Pharmaceuticals Introduce Strategies to Improve Immunotherapy Against Cancer

–  Local Delivery of Checkpoint Control Antibodies Greatly Improve Efficacy and Safety

–  Promising Potential for Combinatorial Strategies

ISA Pharmaceuticals B.V., a clinical-stage immunotherapy company focusing on rationally designed therapeutic vaccines against cancer and persistent viral infections, today announced the publication of three peer-reviewed papers that demonstrate the benefit of local delivery of a checkpoint control antibody targeting CTLA-4 (cytotoxic T lymphocyte antigen-4) for the successful eradication of cancer and the reduction of side effects. The papers include a review that underlines the importance of strategies for combinatorial treatments to improve further the immunotherapy of cancer. ISA Pharmaceuticals is developing cancer immunotherapies along those lines, in particular its Synthetic Long Peptide (SLP®) vaccine ISA101 for the treatment of HPV-induced diseases, such as cervical cancer and head and neck cancer, and ISA203 for the treatment of various tumors including lung cancer, head and neck cancer, breast cancer and melanoma.

In a paper just published in Clinical Cancer Research [1], a team of scientists from Leiden University Medical Center (LUMC) and ISA Pharmaceuticals report that in preclinical mouse models of cancer, the injection of a CTLA-4 blocking antibody in a slow-release formulation close to the tumor is very effective in activating a systemic anti-tumor (CD8+) T cell response. CTLA-4 is a crucial immune checkpoint protein that down-regulates the body’s immune response. The low-dose local treatment (50μg subcutaneously in a slow-release vehicle) eradicates tumors, including distant tumors, as effectively as a high-dose systemic treatment (2×200μg intraperitoneally). The method also leads to a 1000-fold decrease of antibody levels in the serum, thereby reducing adverse events and the risk of autoimmunity.

These findings are supported by an increasing number of studies demonstrating that local targets, mainly present in the microenvironment of tumors and draining lymph nodes, are key players in tumor progression. As published in a second paper by researchers from LUMC and ISA, a review in the International Journal of Cancer [2], local immunotherapies have clear advantages over systemic treatments, both in their ability to shift tumor-promoting mechanisms towards effective tumor-eradicating immunity and in terms of reducing the risks of systemic administration.

In the third publication in Seminars in Immunology [3], current cancer immunotherapy approaches are reviewed, concluding that most standalone immunotherapeutic strategies either fail to affect progressive diseases and survival significantly – or only do so in a minority of patients. The authors support combinations of synthetic vaccines that stimulate tumor-specific T cell responses and adjuvants, immune-modulating antibodies, cytokines, or chemotherapy.

 

[1] Fransen MF et al. (2103), Clin Cancer Res, Published Online First June 20, 2013; doi: 10.1158/1078-0432.CCR-12-0781

[2] Fransen MF et al. (2013), Int. J. Cancer, 132: 1971–1976; doi: 10.1002/ijc.27755

[3] Arens R et al., (2013), Sem Immunol, Published Online First May 21, 2013;
doi: 10.1016/j.bbr.2011.03.031

Food for Thought: Weekly Wrap-Up

This week, Frankfurter Allgemeine Zeitung (FAZ) deals with potential origins of the enterohemorrhagic E. coli (EHEC) epidemic in Germany. Christina Hucklenbroich details the consequences of feeding cattle mixed provender, a forage that changes the environment of the intestinal tract so that it becomes an ideal habitat for bacteria like E. coli. In a separate article the same author deals with an EHEC outbreak in 1997 in the US which affected mostly women – similar to the current epidemic in Germany. Back then, the source had been alfalfa sprouts used in salads. While the ultimate source had never been found, scientists suspected that already the seeds had been contaminated. Richard Friebe, also in FAZ, deals with slurry from pigs, cattle, and fowl that is know to contain all sorts of bacteria and viruses. It is used either directly as fertilizer (though not on vegetables and salad plants) or may contaminate adjacent fields through spillover, spray or via irrigation using water contaminated with slurry.

Susanne Kutter in Wirtschaftswoche introduces Holger Zinke, co-founder and CEO of BRAIN AG, a biotech company specialized on “white” biotechnology, using the skills of microbes to re-design industrial processes or to come up with entirely new ones. Thereby, pharma and chemical industry can save energy, money, and expenses for raw materials. The article is part of a series on pioneers of the “greentech-era”, trying to change the industry to make it more energy-efficient and sustainable.

In Forbes, Matthew Herper analyses why scientists in Germany and China used small desktop sequencers by Ion Torrent rather than big machines by Illumina, Life or 454 Life Sciences to decipher the sequence of the EHEC strain rampaging through Germany. Herper claims it is speed and cost. However, the choice was also influenced by the fact that the sequence of the new strain matched strains with sequences available in public databases relatively closely so that puzzling together the short sequence data generated by the machine was easy.

In reporting on this year’s annual conference of the American Society of Clinical Oncology (ASCO), Andrew Pollack in The New York Times (NYT) introduces two drugs for the treatment of melanoma: vemurafenib (developed by Genentech, part of Roche Group), which attacks a specific mutation accelerating tumor growth and Yervoi ipilimumab (developed by Bristol-Myers Squibb), which unleashes the body’s immune system to fight the cancer. Yervoi was approved by FDA in March this year. Pollack also features latest clinical results for Aromasin exemestane, a drug marketed for preventing recurrences of breast cancer.

Gina Kolata, also in NYT, deals with the phenomenon of “linguistic toxicity”, i.e. drug labels listing more and more side effects, even contradictory ones such as that a medication can cause diarrhea or constipation. As of today, drug labels in the US list an average of 94 side effects (the top numbers already are exceeding 500), despite efforts of FDA to make drug makers avoid listing of side effects that are infrequent and minor, commonly observed in the absence of drug therapy or not plausibly related to drug therapy. Main reason is pharma companies trying to protect themselves against lawsuits.

Last not least, New Scientist features the latest advice for those of you on diet: psychologist found that if you succeed convincing yourself that everything you eat bears enormous amounts of calories, your ghrelin hormone level will drop much lower after eating so that you feel being full faster.