More on immune based therapies for the treatment of cancers

ImmunoCellular Therapeutics Retains Services of Torrey Pines Institute for Molecular Studies and Renowned Immunologist to Evaluate Lead Product Candidate, Business Wire, July 14, 2009. Excerpts:

ImmunoCellular Therapeutics, Ltd. (OTCBB: IMUC), a clinical-stage biotechnology company that is developing immune based therapies for the treatment of brain and other cancers, announced today that it has retained the services of the Torrey Pines Institute for Molecular Studies in San Diego, CA, to evaluate the immunogenicity of peptides to target cancer stem cells (CSC’s) relating to the Company’s lead product candidate ICT-121. The evaluation will be conducted by Dr. Clemencia Pinilla, a specialist in immune response mechanisms and their role in the prevention and cause of human disease with over 100 publications and multiple patents to her credit.

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ICT-121 is IMUC’s cancer stem cell (CSC) vaccine product candidate that consists of a peptide to stimulate a cytotoxic T-lymphocyte (CTL) response to CD133, which is generally overexpressed on the CSCs.

Relevant links: Profile of Clemencia Pinilla, of the Torrey Pines Institute for Molecular Studies in San Diego, California; and, Opinion: A Stem of Hope for Cancer Treatments by Manish Singh (President and CEO of IMUC), Genetic Engineering & Biotechnology News, June 12, 2009. [Previous blog post: Bright future for CSC therapies?, June 14, 2009].

Note that it is important that CSC-targeted vaccination "should not lead to immune reaction to normal cells that may express common antigens". For a recent publication from which this quotation is taken, see: Antigen-Specific T Cell Response from Dendritic Cell Vaccination Using Cancer Stem-like Cell-Associated Antigens by Qijin Xu and 8 co-authors, including John S Yu, Stem Cells 2009(Apr 23) [Epub ahead of print][PubMed Citation]. (John S Yu is Chief Scientific Officer and Chairman of the Board of IMUC, see: Our Team - IMUC).

For some background about immune based therapies for the treatment of cancer, see: Cancer Vaccines by Preeti Gokal Kochar, ProQuest Discovery Guide, January 2006.

See also: Connotea bookmarks matching tag CD133.

Bright future for CSC therapies?

Opinion: A Stem of Hope for Cancer Treatments, Manish Singh, Genetic Engineering & Biotechnology News, June 12, 2009. Excerpts:

Three Attack Strategies
Investigations currently in progress target cancer stem cells using one of three approaches: small molecules, mAbs, or vaccines. Small molecule therapies work by perturbing the signaling pathway of cancer stem cells to put brakes on tumorogenesis. mAbs, on the other hand, are focused on recognizing certain markers that are highly expressed on CSCs but not on normal cells or normal stem cells. Lastly, active immunotherapy utilizes the native immune system to recognize and destroy cancer stem cells while leaving normal cells intact. While a few companies have been started de novo to focus on these programs, a number of existing compounds are also being tested for their effect on cancer stem cells.

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Our understanding of stem cells is in its infancy today, but there can be no doubt about their potential to solve some of the most complicated health problems in both regenerative medicine as well as cancer. Regenerative medicine is much more complicated due to several stages of development that the stem cells have to undergo to regenerate tissue. However, it may be easier to find therapeutic application in cancer, where the goal is to capture and destroy these tumor-initiating stem cells. Based on several encouraging clinical and preclinical studies combined with significant interest from large pharma to acquire these early-stage assets even before they enter the clinic, a bright future may be in store for cancer stem cell therapies.

CIRM videos on YouTube

There's an Announcement, dated January 20, 2009, on the home page of the California Institute for Regenerative Medicine (CIRM), entitled: CIRMTV: CIRM videos now available on YouTube. The link leads to a Playlist of CIRM Video Stem Cell Basics. One of these, Therapies Based on Cancer Stem Cells (4:33 min), features Catriona Jamieson. It currently has a 5-star rating.

For an example of a news release about the work of her group, dated April 7, 2008, see: From Bench to Bedside in One Year: Stem Cell Research Leads to Potential New Therapy for Rare Blood Disorder by Debra Kain, University of California - San Diego News Center. The first sentence:

A unique partnership between industry and academia has led to human clinical trials of a new drug for a rare class of blood diseases called myeloproliferative disorders (MPD), which are all driven by the same genetic mutation and can evolve into leukemia.

This research was funded in part by a grant from CIRM.

Guidelines for the Clinical Translation of SC

Guidelines for the Clinical Translation of Stem Cells, International Society for Stem Cell Research (ISSCR), December 3, 2008. Links are provided to the Guidelines [PDF], to Apppendix 1 (a Patient Handbook on Stem Cell Therapies) [PDF], to Appendix 2 (Additional Resources), to a Cell Stem Cell article summarizing the essential elements of the document [PubMed Citation] and to a joint ISSCR and Cell Stem Cell Press Release about the Guidelines.

For an article, in the same issue of Cell Stem Cell, that provides evidence that such Guidelines are needed, see: Stem Cell Clinics Online: The Direct-to-Consumer Portrayal of Stem Cell Medicine by Darren Lau and 5 co-authors, including Timothy Caulfield, Cell Stem Cell 2008(Dec 4); 3(6): 591-4. PubMed Abstract:

Despite the immature state of stem cell medicine, patients are seeking and accessing putative stem cell therapies in an "early market" in which direct-to-consumer advertising via the internet likely plays an important role. We analyzed stem cell clinic websites and appraised the relevant published clinical evidence of stem cell therapies to address three questions about the direct-to-consumer portrayal of stem cell medicine in this early market: What sorts of therapies are being offered? How are they portrayed? Is there clinical evidence to support the use of these therapies? We found that the portrayal of stem cell medicine on provider websites is optimistic and unsubstantiated by peer-reviewed literature.

See also: Laws needed to protect patients from stem cell clinics' exaggerated claims: study by Sheryl Ubelacker, Canadian Press, December 3, 2008. The first sentence:

Canadians should be "very skeptical" of foreign clinics that use websites to promote stem cell therapies for a wide range of medical conditions, warn researchers, saying there is a dearth of scientific evidence to back up their claims.

Comments: The Guidelines contain no explicit mention of cancer SC. However, if one accepts the prediction that "diagnostic methods based on the detection of CSC’s will have the potential to address key limitations of current methods" [excerpt from Business Wire, April 26, 2007], then some attention needs to be paid to the known limitations of diagnostic methods. Two examples of relevant references:

1) Grading quality of evidence and strength of recommendations for diagnostic tests and strategies by Holger J Schünemann and 10 co-authors, including Gordon H Guyatt, BMJ 2008(May 17); 336(7653): 1106-10 [PubMed Citation]. Excerpt from the publicly-accessible Extract:

Inferring from data on accuracy that a diagnostic test or strategy improves patient-important outcomes will require the availability of effective treatment, reduction of test related adverse effects or anxiety, or improvement of patients’ wellbeing from prognostic information.

Excerpt from the full text:

Although recommendations on diagnostic testing share the fundamental logic of recommendations on treatment, they present unique challenges.

2) See also: Evaluation of clinical innovation: a gray zone in the ethics of modern clinical practice? by Johane Patenaude and 4 co-authors, J Gen Intern Med 2008(Jan); 23(Suppl 1): 27-31 [PubMed Citation]. Excerpt for the Conclusions section of the (publicly accessible) full text:

Innovation is a neglected area for ethics assessment. Further studies on a larger scale are necessary to review the concepts of experimental, innovative, and commonly accepted care.

Perhaps a subsequent version of the ISSCR Guidelines should include a section on diagnostic tests involving CSC?