Tag: lung cancer

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

Can bioplastics, which is derived from renewable resources and biodegradable, become an alternative to conventional plastics made from mineral oil? Not yet, writes Nina Weber in Der SPIEGEL. Cultivation of raw material needs pesticides and fertilizers and the predominant bioplastics used to date is made from polylactic acid (PLA), which is biodegradable only at high temperatures. The prospects may become better – but only if PLA can be derived from plant remains and if enough PLA is on the market so that recycling is profitable.

Gardiner Harris in The New York Times reports on flaws in a widely cited lung cancer study involving more than 50,000 patients. The study’s conclusion that  80% of lung cancer deaths could be prevented through wide use of CT scans made the headlines in 2006. Now it seems that the researchers are unable to locate 90% of the consent forms so that  a confidential report evaluating the study on behalf of the lead study center recommend that the trial be stopped already in 2008. The study is still ongoing.

The New Scientist reports on findings that the malaria parasite Plasmodium falciparum can be killed by kinase inhibitors, common anti-cancer drugs. In in-vitro experiments at Lausanne Federal Polytechnic in Switzerland researchers exposed malaria-infected liver and blood cells to kinase inhibitors and observed that some of these compounds selectively killed the parasite, but not the cells.

Also in New Scientist, Ahmed Zewail, who won the Nobel prize in chemistry in 1999, claims that the Middle East is ripe for a scientific revolution.  At present, he states, Arab, Persian, and Turkish scientists as a group are underperforming as compared to colleagues in the West or Far East. Zewail thinks that the recent revolutions will open the door to improve on literacy, women’s participation and education and bear the chance to remove red tape and allow freedom of thought. He calls on partnering with Muslim countries to establish centers of excellence in science and technology.

Finally, Alex Knapp in Forbes introduces Justin, an impressive humanoid robot made in Germany by DLR, the German aerospace agency. So far, this incredible piece of German hard- and software engineering is used to catch two balls at once while making coffee. the akampioneer very much hopes he will learn better tricks to avoid the “invented in Germany, marketed elsewhere” pitfall.