A Vaccine May Cause Pancreatic Cancer to Respond to Immunotherapy

Editor’s note: Immunotherapy treatments, which boost a patient’s own immune system to fight cancer, are a very promising area of research. However, pancreatic ductal adenocarcinomas (PDAC) tend not to respond to immunotherapy. New research shows that PDAC tumors could potentially be primed to respond better to immunotherapy by treating them with a vaccine and low-dose chemotherapy before surgery to remove the tumor.

“Pancreatic ductal adenocarcinomas (PDAC) do not typically respond to immunotherapy, which limits treatment options for this cancer. By priming with a therapeutic vaccine and a low-dose chemotherapy combination prior to surgery, researchers converted PDACs into immunogenic cancers that may respond to immunotherapy, according to a study published in Cancer Immunology Research, a journal of the American Association for Cancer Research (produced in collaboration with the Cancer Research Institute).

” ‘The only curative treatment for pancreatic cancer is complete surgical resection, and approximately 80 percent of patients who undergo surgery relapse and die from the disease within five years, suggesting a need for effective strategies,’ said Lei Zheng, MD, PhD, assistant professor of oncology and surgery at the Sidney Kimmel Comprehensive Cancer Center and the Skip Viragh Center for Pancreatic Cancer Research and Clinical Care at the Johns Hopkins University School of Medicine in Baltimore.”

“In this clinical trial, pretreatment of PDAC patients with the vaccine GVAX and low doses of the chemotherapy cyclophosphamide caused the aggregation of immune cells inside the patients’ tumors, and many of these immune cells expressed proteins that may make these cancers amenable to immunotherapies such as PD-1 inhibitors.”


Agenus Brain Cancer Vaccine Nearly Doubles Survival Rate in Study

“Agenus Inc said its experimental cancer vaccine helped brain tumor patients live nearly twice as long compared with those who received standard of care treatment…

“The drug, when given in addition to standard treatment, extended median overall survival in 50 percent of newly-diagnosed glioblastoma multiforme (GBM) patients to two years in a mid-stage study.

“GBM patients, who tend to succumb to the disease within one year, are usually treated with a combination of radiation and the chemotherapy drug temozolomide.”

Editor’s note: Prophage is a new “cancer vaccine” that might boost a patient’s own immune system to help fight cancer. Cells from each patient’s tumor are used to personalize Prophage specifically for the patient. This article discusses results from a clinical trial testing Prophage in volunteer patients with glioblastoma multiforme (GBM). Some of the patients in the trial were treated with Prophage in combination with standard radiation and chemotherapy treatment, while for comparison, others were treated only with standard radiation and chemo. The results showed that adding Prophage to standard treatment can help some patients live longer.


Planned Clinical Phase I Trial to Examine the Safety of Vaccine Against Gliomas Based on Mutant IDH1 in Human Patients

“Astrocytomas and oligodendrogliomas are subtypes of a brain cancer called ‘glioma’. These incurable brain tumors arise from glial cells, a type of support cell found in the central nervous system. ‘Low-grade gliomas’, which grow comparatively slowly, spread in a diffuse manner across the brain and are very difficult to completely eliminate through surgery. In many cases, the effectiveness of treatments with chemotherapy and radiotherapy is very limited. Gliomas can develop into extremely aggressive glioblastomas.

“Low-grade gliomas have a particular feature in common: more than 70% of the cases exhibit the same gene mutation in tumor cells. An identical ‘typo’ in the DNA causes the exchange of a single, specific protein building block (amino acid) in an enzyme called isocitrate dehydrogenase 1 (IDH1). As a result, most cancer cells do not follow the original building plan for the protein; at the 132nd position in the molecule’s sequence, they insert the amino acid histidine instead of arginine…

” ‘…we might be able to use a vaccine to alert the patient’s immune system to mutant IDH1, fighting the tumor without damaging healthy cells,’ [Prof. Dr. Michael Platten at the German Consortium for Translational Cancer Research] explains.

“In collaboration with a team of physicians and scientists from Heidelberg University Hospital, DKFZ and the Universities of Mainz, Tübingen and Hamburg, Platten and his co-workers have now made the first successful step toward a vaccine that specifically targets the mutation in the tumor.

“In a clinical trial scheduled to start early next year, with the support of the German Consortium for Translational Cancer Research (DKTK), they plan to examine the safety of the vaccine against gliomas based on mutant IDH1 in human patients, for the first time.”

Editor’s note: Early next year, oncologists will begin testing a newly developed cancer vaccine in a clinical trial with volunteer patients, in the hopes that it will help treat low-grade gliomas. Cancer vaccines are a type of immunotherapy treatment; they boost a patient’s own immune system to fight cancer. The new vaccine takes advantage of a dysfunctional protein that is found in 70% of low-grade gliomas. The protein is called IDH1, and the vaccine is designed to alert the patient’s immune system to attack cells with mutant IDH1, potentially shrinking the brain tumor. So far, the vaccine has only been tested in mice, but the results were promising.


Survival Hope for Melanoma Patients Thanks to New Vaccine

“University of Adelaide researchers have discovered that a new trial vaccine offers the most promising treatment to date for melanoma that has spread, with increased patient survival rates and improved ability to stop or reverse the cancer.

“The vaccine, known as vaccinia melanoma cell lysate (VMCL), was given regularly as a treatment to 54 South Australian patients with advanced, inoperable melanoma over a 10-year period.”

Editor’s note: The cancer vaccine VMCL is a type of immunotherapy, which means it boosts a patient’s own immune system to fight cancer.


New Cancer Vaccine Approach Directly Targets Dendritic Cells

“Celldex Therapeutics announced today that final data from its Phase 1 study of CDX-1401 in solid tumors, including long-term patient follow-up, have been published inScience Translational Medicine. The data demonstrate robust antibody and T cell responses and evidence of clinical benefit in patients with very advanced cancers and suggest that CDX-1401 may predispose patients to better outcomes on subsequent therapy with checkpoint inhibitors. CDX-1401 is an off-the-shelf vaccine consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen. The vaccine is designed to activate the patient’s immune system against cancers that express the tumor marker NY-ESO-1. While the function of NY-ESO-1 continues to be explored, references in the literature suggest that its expression might reflect the acquisition of properties that cancers find useful, such as immortality, self-renewal, migratory ability and the capacity to invade.”

Editor’s note: Cancer vaccines like CDX-1401 are a type of immunotherapy, meaning that they boost a patient’s own immune system to fight cancer. CDX-1401 is able to attack tumor cells because the tumor cells have a molecule called NY-ESO-1 that CDX-1401 recognizes. We recently published a story about another treatment that is meant for patients whose tumors have NY-ESO-1. To learn more about how patients can use molecular testing to see if particular treatments might work for them, click here.


New Cancer Vaccine Approach Directly Targets Dendritic Cells

“Celldex Therapeutics announced today that final data from its Phase 1 study of CDX-1401 in solid tumors, including long-term patient follow-up, have been published inScience Translational Medicine. The data demonstrate robust antibody and T cell responses and evidence of clinical benefit in patients with very advanced cancers and suggest that CDX-1401 may predispose patients to better outcomes on subsequent therapy with checkpoint inhibitors. CDX-1401 is an off-the-shelf vaccine consisting of a fully human monoclonal antibody with specificity for the dendritic cell receptor DEC-205 linked to the NY-ESO-1 tumor antigen. The vaccine is designed to activate the patient’s immune system against cancers that express the tumor marker NY-ESO-1. While the function of NY-ESO-1 continues to be explored, references in the literature suggest that its expression might reflect the acquisition of properties that cancers find useful, such as immortality, self-renewal, migratory ability and the capacity to invade.”

Editor’s note: Cancer vaccines like CDX-1401 are a type of immunotherapy, meaning that they boost a patient’s own immune system to fight cancer. CDX-1401 is able to attack tumor cells because the tumor cells have a molecule called NY-ESO-1 that CDX-1401 recognizes. We recently published a story about another treatment that is meant for patients whose tumors have NY-ESO-1. To learn more about how patients can use molecular testing to see if particular treatments might work for them, click here.


Thematic Session 10: Update on treatment options for patients with CRPC

“There are new treatment options for castration resistant prostate cancer (CRPC) but finding the optimal strategy and selecting the right patient is still fraught with challenges and difficulties, according to uro-oncology experts during a thematic session at the 29th Annual EAU Congress in Stockholm, Sweden.

“ ‘With many prostate cancer patients hoping for a better life without symptoms of the disease, the aim is to identify which new drugs, or a combination of these drugs, can offer prolong survival or effectively palliate bone disease,’ said Prof. Maria De Santis who chaired Thematic Session 10.

“The session focussed on castration-resistant prostate cancer (CRPC) which is often considered one of the toughest challenges in uro-oncology since despite repeated treatments the disease accelerates or progresses with severe impact on quality of life (QoL).”

Editor’s note: This article is about an event at a urology conference in Sweden. During the event, participants discussed the latest in prostate cancer treatment, with a focus on castration-resistant prostate cancer (CRPC).


Dendreon Says Prelim. Data from LT Phase II STAND Study Will Be Presented at EAU Congress, Will Show Immune Responses with PROVENGE Enhanced, Sustained

“Dendreon Corporation (NASDAQ: DNDN) today announced the presentation of preliminary data from a long-term analysis of the Phase II STAND study demonstrating that tumor-specific T-cell responses appear to be enhanced and sustained when PROVENGE^® (sipuleucel-T) is given after androgen deprivation therapy (ADT) in patients with biochemically-recurrent prostate cancer (BRPC) at high risk for metastases. These data will be presented at the 29^th Annual European Association of Urology (EAU) Congress taking place from April 11-15, 2014 in Stockholm, Sweden.”

Editor’s note: This story is about a study that demonstrated positive patient responses when the cancer vaccine Provenge was given as a prostate cancer treatment after patients were first treated with androgen deprivation therapy (ADT). The study focused on patients with biochemically-recurrent prostate cancer (BRPC) at high risk for metastasis.


Using a Person's Own Immune System to Fight Cancer: Phase I Clinical Trial of New Immunotherapy Beginning

“Moffitt Cancer Center has initiated a phase I clinical trial for a new immunotherapy drug, ID-G305, made by Immune Design. Immunotherapy is a treatment option that uses a person’s own immune system to fight cancer. It has several advantages over standard cancer therapies, including fewer side effects and an overall better tolerability. It tends to be most effective in patients who have smaller, localized tumors that have not spread to distant sites.”

Editor’s note: This treatment looks for and targets cells that have the protein NY-ESO-1. Only 10-15% of tumors have NY-ESO-1, and patients’ tumors must test positive for NY-ESO-1 in order for the patients to enroll in the trial. Learn more about immunotherapy and clinical trials here.