A Promising New Vaccination Strategy For Late-Stage Melanoma-INCIDENTS-XIYUANLU
A therapeutic cancer vaccine being developed by an international team of cancer immunologists working within the Cancer Research I titute/Ludwig I titute for Cancer Research Cancer Vaccine Collaborative (CVC) succe fully induced a comprehe ive, tumor- ecific immune re o e in patients with late-stage metastatic disease, with results indicating that the vaccine had a favorable impact on disease progre ion in some patients, according to a paper to be published on September 26 in the scientific journal, Proceedings of the National Academy of Sciences USA. The paper is currently available in the journal's online advance edition.
In a two-part, open-label cohort study, patients whose tumors expre ed the immunogenic NY-ESO-1 antigen, most with melanoma, received at least four monthly doses of recombinant vaccinia-NY-ESO-1 and recombinant fowlpox-NY-ESO-1 vaccine, administered alone and together in a prime-boost setting. In a large proportion of the 23 evaluable patients, the vaccine was shown to stimulate both humoral and cellular immune re o es co isting of antibodies, CD8+ and CD4+ T cells ecific to a broad range of NY-ESO-1 antigenic epitopes. Of nine melanoma patients with progre ive stage III/IV disease at the o et of vaccinatio , seven have survived 17-63+ months. One patient with melanoma showed a complete re o e with total regre ion of lesio and remai disease-free 32 months out; another melanoma patient continues to show disease stabilization 31 months out; and several others showed disease stability with delayed progre ion. The only side-effect o erved in the study was temporary redne , swelling, and itching at the injection site.
As a follow-up to this prime-boost vaccination strategy study, a pro ective phase II prime-boost vaccine study in metastatic melanoma is underway. Therion Biologics Corporation of Cambridge, MA, produced the recombinant vaccinia and fowlpox for both studies.
"These results are very encouraging," says Dr. Lloyd J. Old, director of the Cancer Vaccine Collaborative and chairman of the Ludwig I titute for Cancer Research, and a contributing author to the paper. "While this study ca ot tell us definitively about the potential, overall benefit induced by this vaccination strategy, it does give a strong impre ion that, in patients with advanced metastatic melanoma at least, vaccination altered the expected course of the disease."
Jill O'Do ell-Tormey, Ph.D., executive director of the Cancer Research I titute, which provides funding for Cancer Vaccine Collaborative studies like this one, hailed the study as another succe ful step forward in her organization's efforts to develop immune-based a roaches to the treatment, control, and prevention of cancer.
"Evidence is mounting that the cancer vaccines we are studying in the Cancer Vaccine Collaborative are having significant clinical benefit for some patients," Dr. O-Do ell-Tormey says. "While these are at present a small number of individuals, we see real potential for broader-scale impact. The data we are ama ing from this and other CVC studies continue to su ort the rationale for further exploration of the potential of immune-based cancer therapy. In the proce , CVC studies are teaching us some extremely valuable le o about the fundamentals of cancer vaccination."
The Cancer Vaccine Collaborative has previously reported on trials testing several NY-ESO-1 peptides and whole-protein, and is currently evaluating DNA, viral vector, and bacterial vector-based NY-ESO-1 vaccines. Most notably, a CVC team based in Melbourne reported last year on the efficacy of a NY-ESO-1 peptide vaccine used in combination with ISCOMATRIX?adjuvant which seemed to delay recurrence in melanoma patients. That trial prompted the CVC to open a randomized phase II study of the vaccine, which is currently accruing patients in Australia and the UK in order to determine more solidly the vaccine's impact on overall clinical course.
Dr. Elke Jaeger of Krankenhaus Nordwest in Frankfurt, Germany, the paper's primary author, says this study is the first within the CVC to report on the effectivene of recombinant viral-vector antigen delivery mechanisms. "Our results show this vaccination strategy is effective and requires further investigation." Dr. Jaeger, a member of the Cancer Vaccine Collaborative, will share the details of her team's findings with other CVC researchers at their a ual meeting in New York City in early October.
In addition to reporting the ecific study results, the authors of the AS paper also call for a reevaluation of the benchmarks of succe currently a lied to cancer vaccine studies.
"Many cancer immunologists would argue that the succe criteria that have been a lied to chemotherapeutic investigational new drugs, for i tance, are not nece arily those by which immunotherapies should be judged," Dr. Old says.
"Yes, the ultimate endpoint would be complete, long-lasting remi ion, as sometimes ha e in these vaccine studies," Dr. Old says. "However, such cases are at present few and far between. Rather, we are coming to realize and, more importantly, to accept that a more realistic benchmark of clinical succe with immunotherapy is disease stabilization-that is, control of cancer's growth." According to Dr. Old, from what scientists currently understand about cancer immunosurveillance and immunoediting, vaccine-related stabilization of cancer would corre ond to returning the body from a state of tumor escape to a state of tumor equilibrium.
"Disease stabilization as a succe ful clinical outcome makes se e when talking about immunotherapy," Dr. O'Do ell-Tormey says, "e ecially at this early stage in the development of this new a roach to treating cancer. We have a long way to go, and the Cancer Vaccine Collaborative is doing a lot to move us along as quickly as po ible, but we've got to take things one step at a time."
"We can't say for certain until further studies are carried out," Dr. O'Do ell-Tormey says, "but it does seem that cancer vaccines like those being studied in the Cancer Vaccine Collaborative are potentially extending lives for many patients. Given the negligible toxicity of these therapies and the relative ease with which they're administered to the patient, I'm betting that any cancer patient you talk to would co ider any delay in disease progre ion a succe , too."
About the Cancer Vaccine Collaborative
The Cancer Vaccine Collaborative (CVC) is an i ovative partnership between two not-for-profit i titutio , the Cancer Research I titute and the Ludwig I titute for Cancer Research. Each of these i titutio has a long and distinguished history in the field of cancer immunology and each is committed to tra lating laboratory discoveries in this field into therapeutic cancer vaccines. Begun in 2001, the CVC presently su orts and directs network of coordinated early-phase cancer vaccine trials at 17 ho itals and medical centers around the world. These multiple yet parallel trials use defined antige , standardized treatment protocols, uniform monitoring methodologies, and centralized data collection to provide comparable results that are teaching us how to effectively immunize agai t cancer.
About the Cancer Research I titute
The Cancer Research I titute (CRI) is the world's foremost non-profit, private organization dedicated exclusively to the development of immune-based therapies for the prevention and control of cancer. Guided by a world-renowned Scientific Advisory Council that includes five Nobel Prize wi ers, twenty-eight members of the National Academy of Sciences, and twenty-three members of the Academy of Cancer Immunology, CRI su orts the finest cutting-edge cancer research at top medical centers and universities throughout the world. As the initiator and steward of u recedented global scientific and clinical collaboratio , the Cancer Research I titute is ushering in a new era of scientific progre , hastening the discovery of effective cancer vaccines and other immune-based therapies that are providing new hope to cancer patients. CRI has co istently earned an A grade or higher for fiscal disclosure and efficiency from the American I titute of Philanthropy and top marks from other charity watchdog organizatio . http://www.cancerresearch.org.
About the Ludwig I titute for Cancer Research
The Ludwig I titute for Cancer Research (LICR) is the largest international academic i titute dedicated to understanding and controlling cancer. Headquartered in New York and with one Centre for Clinical Sciences and nine Branches in seven countries, the scientific network that is LICR quite literally a the globe. LICR has developed an impre ive portfolio of reagents, knowledge, expertise, and intellectual property, and has also a embled the perso el, facilities, and practices nece ary to patent, clinically evaluate, lice e, and thus tra late, the most promising a ects of its own laboratory research into cancer therapies.
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