Cancer Vaccines: Stimulating the Immune System to Attack Lymphoma
What if, rather than receiving one-size-fits-all anticancer drugs, patients were treated with specially formulated treatments made to target their own cancer cells? What if patient’s own cancer and immune cells were actually used to develop a treatment just for their cancer?
Instead of suffering the side effects of cancer therapy that damage normal, healthy cells in addition to destroying cancer, patients may find that their own, personalized treatment is accompanied by relatively few discomforts. And, in place of the toxicity of conventional cancer treatment, their personalized therapy would stimulate their own immune system to attack cancer.
These concepts sound both far-fetched and compelling. In fact, personalized medicine has already impacted cancer treatment in the form of targeted therapy—treatment directed toward cancers with certain characteristics. Examples include Herceptin® (trastuzumab), a drug that targets breast cancers that overexpress the HER2 protein; Xalkori® (crizotinib), a drug that targets lung cancers with an ALK gene mutation; and Zelboraf® (vemurafenib), a drug that targets melanomas with a BRAF gene mutation.
Personalized Medicine’s Quest to Utilize the Patient’s Own Immune System
Stimulating the immune system to attack unwanted substances is not a new concept; vaccines, which have traditionally been used to prevent infectious diseases such as measles and the flu, work in this way. What is new, however, is applying this idea to cancer treatment with the development of immunotherapies, or treatments that stimulate the immune system to attack cancer.
Cancer cells are formerly normal cells that have gone awry. However, the immune system—the body’s natural defense against disease—does not distinguish cancer cells from normal cells. This is why cancer is allowed to grow; the immune system does not attack cancer cells because it fails to recognize them as foreign and harmful.
The goal of immunotherapy is to help the body to recognize cancer cells as a threat and activate immune cells to attack the cancer. This is accomplished by working with the normal mechanisms of the immune system that allows it to recognize and target foreign invaders, such as viruses. For this reason, cancer immunotherapies may also be called cancer vaccines.
Antigens Are the Key
All cells have unique proteins or bits of protein on their surface called antigens. Many types of cancer have specific antigens that are present in abundance on their cell surface, which distinguishes them from normal cells. Immunotherapies work in two ways: First, they alert the immune system that cancer-specific antigens—or antigens that are abundantly present on cancer cells—are foreign. Second, immunotherapies stimulate the immune cells to attack cells that have these antigens on their surface.
First to Be Approved: Provenge
Provenge® (sipuleucel-T) was approved by the U.S. Food and Drug Administration (FDA) in 2010. It is intended for the treatment of metastatic, hormone-refractory prostate cancer that is producing few or no symptoms. Metastatic prostate cancer refers to prostate cancer that has spread to other parts of the body, and hormone-refractory prostate cancer is prostate cancer that has stopped responding to hormonal therapy.
Provenge is custom-made for each patient. First, a patient’s immune cells are collected and exposed to a protein that is found in most prostate cancers, linked to an immune-stimulating substance. Next, the patient’s own cells are returned to the patient to stimulate an immune response against the cancer. Provenge is given intravenously (into a vein) in three doses. Common side effects include chills, fatigue, fever, back pain, nausea, joint ache and headache.
Zenocutuzumab - the first approved systemic therapy for patients with NRG1 fusion–positive NSCLC or pancreatic adenocarcinoma.
Zenocutuzumab targeted therapy approved for treatment of pancreatic ductal adenocarcinoma and non-small cell lung cancer with NRG1 fusions.
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Adjuvant therapy with Imfinzi (durvalumab) significantly improved survival outcomes for patients with limited-stage SCLC
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Immunotherapies in Development
There has been much progress in recent years in developing vaccines for the treatment of cancer. The following are just a few of the vaccines that are producing promising results:
BiovaxID® has produced promising results in a Phase III clinical trial of patients with advanced follicular lymphoma.[1] BiovaxID is an individualized vaccine that is made by isolating proteins from a patient’s cancer cells and combining them with a delivery agent and a growth factor. Once injected, the vaccine stimulates immune cells to recognize and fight cancer cells that may be in the body. Among patients with advanced lymphoma who had achieved and maintained a complete remission after chemotherapy, use of BiovaxID significantly delayed cancer progression.
NeuVax™ is made up of a part of the HER2 protein called the E75 peptide. HER2-contributes to the growth of some breast cancers. HER2-targeted therapies such as Herceptin have dramatically improved outcomes for women with HER2-positive breast cancer, but these treatments are generally not used for women whose cancer is only weakly positive for HER2. For women who show some level of HER2 but are not candidates for Herceptin, NeuVax may reduce the risk of breast cancer recurrence.[2]
HSPPC-96 has shown promise in the treatment of glioblastoma multiforme—an aggressive type of brain tumor. The vaccine is created from patient’s own tumor cells. In a Phase II clinical trial of patients with recurrent glioblastoma (glioblastoma that has returned after prior treatment), median survival was 47 weeks. This is longer than the 32 weeks that was observed in similar patients who received other treatments.[3]
DCVax®-L is also being studied for the treatment of glioblastoma, and uses a patient’s own cancer and immune cells. The vaccine is being evaluated in a Phase III clinical trial of people with newly diagnosed glioblastoma who are candidates for surgery. In addition to the vaccine or a placebo, study participants will receive standard treatment with surgery, radiation therapy, and Temodar® (temozolomide).
AGS-003 has been studied most extensively in kidney cancer. The vaccine is developed from a patient’s own tumor and immune cells. In a Phase II trial of patients with metastatic kidney cancer (kidney cancer that has spread to other parts of the body), treatment with a combination of AGS-003 and Sutent® (sunitinib) resulted in longer survival than would be expected with Sutent alone.[4]
Stimuvax is being studied in patients with Stage III non-small cell lung cancer (NSCLC). The goal of this vaccine (also called L-BLP25) is to produce an immune response against cells that express the antigen MUC1, which is widely and abnormally expressed on NSCLC cells. Phase III trials are underway.
References:
[1] Schuster SJ, Neelapu SS, Gause BL et al. Vaccination with patient-specific tumor-derived antigen in first remission improves disease-free survival in follicular lymphoma. Journal of Clinical Oncology. 2011;29:2787-94.
[2] Mittendorf EA, Clifton GT, Holmes JP et al. Clinical trial results of the HER-2/neu vaccine to prevent breast cancer recurrence in high-risk patients: from US Military Cancer Institute Clinical Trials Group Study I-01 and I-02. Cancer. 2012;118:2594-602.
[3] Parsa AT, Crane C, Han S et al. A Phase 2 Multicenter Trial of Autologous Heat Shock Proteinpeptide Vaccine (HSPPC-96) for Recurrent Glioblastoma Multiforme (GBM) Patients Shows Improved Survival Compared to a Contemporary Cohort Controlled for Age, KPS and
Extent of Resection. Presented at the 2012 Annual Scientific Meeting of the American Association of Neurological Surgeons.Miami, FL. April 14-18, 2012. Abstract 704.
[4] Figlin RA, Amin A, Dudek A et al. Phase II study combining personalized dendritic cell (DC)-based therapy, AGS-003, with sunitinib in metastatic renal cell carcinoma (mRCC). Presented at the 2012 Genitourinary Cancers Symposium.San Francisco, CA. February 2-4, 2012. Abstract 348.
