This article is the second in a five-part series about emerging vaccines for multiple myeloma. It provides an introduction to the various types of vaccines that are currently under development for myeloma. The first article in the series provided an introduction to the concept of a myeloma vaccine. The third article describes vaccines for which clinical trials have been completed, the fourth article focuses on ongoing and future vaccine research, and the fifth article tells the story of a patient who participated in a myeloma vaccine clinical trial.
As described in Part 1 of this series, there are a number of challenges associated with cancer vaccines. Therefore, a variety of strategies are currently being explored for the development of an effective myeloma vaccine. The following are some of the strategies being tested in laboratory and clinical research.
Protein Vaccines
Many current preventative vaccines, such as the hepatitis B virus (HBV) vaccine, are protein vaccines. These vaccines are comprised of proteins that are contained within a pathogen or toxin. Similarly, the protein-based vaccines currently being explored for multiple myeloma are comprised of proteins unique to cancerous cells.
It is thought that these vaccines work when specialized cells in the immune system ingest the vaccine proteins. These cells can then activate other components of the immune system, which produce antibodies and help fight disease.
Wilm’s tumor gene (WT1) and human telomerase reverse transcriptase (hTERT) are proteins found in a variety of malignancies, including myeloma. The overproduction of these proteins allows cells to rapidly divide and become cancerous. Protein vaccines are currently being developed with WT1 and hTERT for a variety of therapeutic cancer vaccines.
Abnormal production of another protein called Mucin1 (MUC1) also plays a role in the development of multiple myeloma. The use of this protein in a multiple myeloma vaccine has shown promise in preclinical trials and is currently in Phase 1/2 clinical testing.
In addition to finding the correct protein to use for vaccination, much research is focused on compounds that help activate the immune system at the time of vaccination. These compounds, called adjuvants, are currently used in preventative protein vaccines, such as the HBV vaccine, to help stimulate a more potent immune response to the selected protein.
Finding the optimal adjuvant and protein combination to stimulate the most potent immune response will continue to be investigated in laboratories and clinical trials.
Cell-Based Vaccines
Many researchers believe that combining protein vaccines with dendritic cells, a type of cell that activates the immune system, may result in more optimal immune responses. In a cell-based vaccine therapy, dendritic cells are collected from a myeloma patient and loaded with cancer-specific proteins, either manufactured proteins or ones from the patient’s blood. These modified cells are then used to vaccinate the patient.
This technique harnesses the patient’s own immune system for potent responses. When the dendritic cells loaded with cancer-specific proteins are injected back into the patient, they can activate other components of the immune system to recognize and destroy cancerous cells.
Cell-based vaccines have shown promise for a variety of cancers. In fact, the currently-approved therapeutic vaccine for prostate cancer is a dendritic cell-based vaccine.
Recently, a Phase 1 clinical trial of a myeloma vaccine that combined myeloma patients’ cancerous cells with dendritic cells yielded favorable results (see related Beacon news).
Antibody Fragment Vaccines
Multiple myeloma is characterized by the overproduction of monoclonal (M)-protein, a type of abnormal antibody. The type of overproduced M-protein, known as the idiotype, is unique to each patient.
Antibody fragment vaccines, known as idiotype vaccines, are custom-designed from a patient’s M-protein in order to stimulate his or her immune system to recognize it. Protein and cell-based formulations of these vaccines are currently being explored.
Idiotype vaccination is one of the most active research areas for multiple myeloma vaccine development to date. Half of all the recently completed clinical trials for multiple myeloma vaccines involve idiotype strategies.
Donor Vaccination And Allogeneic Stem Cell Transplantation
Allogeneic stem cell transplantation, in which a healthy donor’s stem cells are transplanted to a myeloma patient, has long been considered a possible cure for multiple myeloma because the healthy donor cells can destroy myeloma cells.
However, graft-versus-host disease (GVHD) remains a serious and life-threatening complication of the procedure, which limits its clinical use. GVHD occurs when the donated cells view healthy cells in the recipient’s body as foreign and attack them.
One strategy currently being explored to enhance the anti-myeloma effect of allogeneic stem cell transplantation and reduce the severity of GVHD is to target the donor cells to destroy patient cancer cells more selectively.
Therefore, the donor is vaccinated with M-protein fragments isolated from the myeloma patient prior to bone marrow harvest. When the bone marrow is harvested, there will be an increased proportion of cells that target the myeloma patient’s cancerous cells. The resulting transplantation should also result in less severe GVHD.