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New Advances In Myeloma Vaccines – Part 4: Ongoing Research

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Published: Mar 11, 2011 11:57 am

This article is the fourth in a five-part series about emerging vaccines for multiple myeloma. It focuses on ongoing myeloma vaccine research.  The first article in the series provides an introduction to the of a myeloma vaccine, the second article provides an introduction to the various types of myeloma vaccines that are currently under development, and the third article describes vaccines for which clinical trials have been completed.  The fifth article tells the story of a patient who participated in a myeloma vaccine clinical trial.

Vaccine therapy for multiple myeloma is an active area of research. There are currently more than a dozen ongoing clinical trials for myeloma vaccine therapy.  A brief description of each trial will be described in this article.  For more detailed information, please refer to the provided links.

Ongoing Protein Vaccine Trials

Protein-based vaccines currently being explored for multiple myeloma are comprised of proteins unique to cancerous cells (see Part 2 for information about protein vaccines).  There are currently several clinical trials underway exploring the use of these vaccines for the treatment of multiple myeloma.

Two ongoing trials are investigating vaccines based on the protein MAGE-A3. MAGE-A3 is frequently produced by myeloma cells in high-risk patients.

Investigators at the Myeloma Institute for Research and Therapy in Arkansas are actively recruiting patients for a Phase 2/3 clinical trial of the MAGE-A3 protein vaccine. The study will enroll approximately 100 myeloma patients.

During the trial, patients will receive a series of 12 MAGE-A3 vaccinations, which will be injected subcutaneously (under the skin), in combination with a stem cell transplant. Researchers hope to determine the safety and efficacy of repeated MAGE-A3 vaccination during the course of this study. For more information, please see the Myeloma Institute for Research and Therapy website.

The University of Maryland is also conducting a Phase 2 trial of a MAGE-A3 vaccine.  The trial is currently recruiting patients to determine the effects of MAGE-A3 vaccination in conjunction with autologous stem cell transplantation and Revlimid (lenalidomide) maintenance therapy.

In addition to its trial of a MAGE-A3 vaccine, the University of Maryland is also collaborating with the University of Pennsylvania on a Phase 1/2 trial for another therapeutic myeloma vaccine.  Like MAGE-A3, the protein in this vaccine, called hTERT, is found uniquely in cancer.  Researchers have already completed enrollment and are no longer recruiting participants for this trial.

Merck KGaA is currently conducting a Phase 2 clinical trial of Stimuvax (L-BLP25) for the treatment of multiple myeloma. Stimuvax is a vaccine comprised of the MUC1 protein. MUC1, which is associated with tumor progression, is present in a variety of both solid and non-solid tumors. Stimuvax is also in Phase 3 clinical trials for the treatment of lung cancer.

Vaxil Biotherapeutics is also developing a MUC1-based myeloma vaccine, called ImMucin. The company is currently recruiting myeloma patients for a Phase 1/2 clinical trial of ImMucin.

Preclinical studies have shown that ImMucin is able to generate immune responses specific to MUC1-expressing tumors. According to the company’s preclinical trial reports, ImMucin stimulated better immune responses following vaccination than Stimuvax.

The Phase 1/2 clinical trial will begin to test ImMucin’s safety and efficacy in people at the Hadassah Medical Center in Jerusalem. For more information, see the Vaxil Biotherapeutics website.

The company Celldex Therapeutics is developing a vaccine: CDX-1401.  It is based on a protein called NY-ESO-1, which is uniquely found in tumor cells.  The Phase 1/2 clinical trial is currently recruiting patients to study the safety, immune response, and anti-tumor activity of the vaccine.  For more information, see the Celldex Therapeutics website.

Ongoing Cell-Based Vaccine Trials

Cell-based vaccines are designed using cells isolated from the immune systems of patients or donors (see Part 2 for information about cell-based vaccines).  Cell-based vaccines are a very active area of research, and trials investigating cell-based vaccines make up more than half of those being currently conducted.

One promising anti-myeloma vaccine has been developed by combining myeloma tumor cells with dendritic cells, a type of cell that helps activate the immune system. When administered to patients, the vaccine stimulates the immune system to attack and kill the tumor cells.

A dendritic cell-based vaccine is currently in Phase 1/2 clinical trials.  The trial, being conducted by an institute in Poland in collaboration with the National Cancer Institute, is recruiting myeloma, leukemia, and lymphoma patients.

A Phase 1 trial is also being conducted at the Mount Sinai School of Medicine in New York to determine the efficacy, safety, and feasibility of a dendritic cell-based vaccine after stem cell transplantation.   Myeloma and lymphoma patients are being recruited for the trial.

Two clinical trials are currently underway in efforts to improve the efficacy of dendritic cell-based vaccines.

The first, a Phase 2 trial being led by researchers at the Beth Israel Deaconess Medical Center, is currently recruiting patients.  It will investigate the efficacy of dendritic cell vaccination when administered with an antibody that may enhance the anti-tumor immune response.

Similarly, a Phase 2 study being conducted at the Mayo Clinic will determine what effect two immune response enhancing proteins will have when administered with a dendritic cell-based vaccine.

The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University is currently heading two clinical trials for the development of cell-based cancer vaccines that do not involve dendritic cells.  In a Phase 1/2 trial, researchers hope to determine the efficacy of chemotherapy followed by cell-based vaccination and stem cell transplantation for the treatment of newly diagnosed multiple myeloma patients.  In a Phase 2 trial currently recruiting patients, researchers will administer an additional type of immune cell with the myeloma vaccine to determine its effects on anti-myeloma response rates.

Two Phase 2 trials are underway to investigate the use of donor vaccination in the treatment of multiple myeloma.  In this strategy, a donor is vaccinated with monoclonal (M)-protein fragments isolated from the myeloma patient.  The patients then receive either a stem cell transplant or immune cell infusion using the donors’ cells.  Stem cell transplants using this type of vaccination should also result in less severe graft-versus-host disease (see Part 2 for information about donor vaccination).

The first donor vaccine study is a Phase 2 study being conducted at the M.D. Anderson Cancer Center in Houston, which is currently recruiting myeloma patients who relapsed or did not achieve a complete response after a donor stem cell transplant.  During the trial, the donor and patient will both be vaccinated, and then the patient will be infused with immune cells from the donor.

The other Phase 2 study, which is being conducted at the National Cancer Institute, is studying donor vaccination followed by stem cell transplantation for myeloma patients using stem cells from their donors.

Although numerous research endeavors for a multiple myeloma vaccine have been completed and are ongoing, medical professionals are cautiously optimistic.  Dr. Maurizio Bendandi, a physician currently conducting myeloma vaccine research at the University of Navarra in Spain, said to the Beacon that for most cancer vaccines there has been a “lack of clear cut demonstration of clinical benefit in large scale clinical trials.” Despite these facts, Dr. Bendandi and many others continue to search for the effective solution.

Photo by Wesley Carter of the U.S. Air Force on Wikipedia - this image is in the public domain.
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