What Are Vaccines and How Do They Work in Myeloma?
The first vaccine ever used was in 1786 for smallpox. Since then, vaccines have become a commonplace way to help prevent disease and most are familiar with how they work. For these types of vaccines, a person is injected with an inactive state of a specific virus in order to aid the person's immune system in developing a defense against that disease. If they work to prevent the flu or pneumonia, could they also be used for cancer?
Today there are two types of cancer vaccines available: preventive and treatment. Treatment vaccines treat an existing cancer by strengthening the body's natural immune response to the cancer. Preventative vaccines help prevent the disease from occurring in the first place, for example the HPV vaccine for cervical cancer.
In myeloma, vaccines have not yet been used successfully to treat myeloma, or reduce the tumor burden when there is a lot of cancer. Vaccines encourage the immune system to get moving to kill myeloma and when large tumor burdens are present, the vaccine can't outrun the pace of the cancer.
The vaccines educate the immune system. When the vaccine is given, the patient's T cells recognize it as a foreign protein, and therefore suppress the production of myeloma cells and the potential of becoming active in the future.
The goal of today's myeloma vaccines in clinical trials are to prevent progression for early conditions like MGUS or smoldering myeloma, or prevent relapse after standard treatments like stem cell transplant.
For many of these vaccines, they are used in combination with lenalidomide, which can boost specific immune functions.
Precursor Condition Vaccines to Prevent Progression
A peptide vaccine called PVX-140 is in clinical trials to see if it can prevent smoldering myeloma from progressing to active myeloma. The safety, tolerability and impact of the PVX-410 vaccine in smoldering myeloma look promising. This vaccine is being used in 3 smoldering myeloma studies with several other drugs including an HDAC inhibitor. This vaccine is also being used in triple negative breast cancer studies.
PVX-410 is an investigational, HLA A2 restricted, multi-peptide vaccine designed to induce a T cell mediated immune response (CD8 +, cytotoxic lymphocytes or CTLs) to tumor cells by selectively stimulating tumor-associated antigen-specific CTLs to the tumor antigen targets (XBP1, CD138, CS1). These tumor antigen peptides stimulate antigen-specific CTLs which demonstrate tumor-specific T lymphocyte responses including T cell proliferation, IFN‑γ secretion, and cytotoxic activity. CTL activation specific to PVX-410 has been demonstrated in vitro to patient tumor cells (MM/SMM) and tumor cell lines (MM, breast, colon, prostate, pancreatic and AML) and in a phase 1b clinical trial with smoldering myeloma patients who were HLA A2 positive. PVX-410 is now being evaluated in 3 on-going combination treatment studies with and HDAC inhibitor in smoldering myeloma and in combination with checkpoint antibodies for the treatment of adjuvant and metastatic triple negative breast cancer.
Vaccines for Patients in Active Treatment
There are vaccines in development for patients in active treatment. The goal here is to extend remissions following standard treatment, such as stem cell transplant or triplet combinations.
Dr. David Avigan at Beth Israel Deaconness is working on a personalized dendritic cell vaccine for patients following stem cell transplant. The goal is to extend the time of remission for these patients.
Likewise, a new GVAX vaccine is also being studied at Johns Hopkins by Dr. Syed Abbas Ali and Dr. Ivan Borrello. This vaccine is used after myeloma therapy when patients have had a good response. This vaccine can be given to transplant patients if it has been one year post-transplant and the vaccine is given with lenalidomide.
The ability to personalize vaccines may lead to new ways of shutting down myeloma before it starts. Sometimes these personalized vaccines are also called "neoantigens" that are customized for each individual patient. MD Anderson Cancer Center is working on a clinical trial to develop these customized neoantigen vaccines for patients with smoldering myeloma to prevent progression.
To learn more about myeloma vaccines, watch the Patient Power video with a discussion from Dr. Noopur Raje of Massachusetts General.