Immunotherapy is a promising new direction in treating cancer. For instance, a clinical study of advanced rectal cancer found that an immunotherapy using monoclonal antibodies to stimulate a strong immune response showed complete effectiveness at one year. All patients in the study had no evidence of cancer at that time. This is especially remarkable since none of the patients needed chemotherapy or surgery after starting on the drug.^[i]

However, immunotherapy has not had similar achievements against prostate cancer (PCa). The year 2010 sparked hope for patients with metastatic prostate cancer when the FDA approved a new type of immunotherapy vaccine using a patient’s own immune cells: Sipuleucel-T (brand name Provenge). Approval was based a clinical trial of 512 patients who were randomly assigned to one of two arms: vaccine or placebo. The vaccine group experienced longer survival (25.8 months for vaccine vs. 21.7 months for placebo). While an additional four months of life may seem small, the potential for immunotherapy as an eventual treatment for all prostate cancers is huge.

It’s now been over a decade since Provenge became available. An enormous research campaign is underway toward developing an immunotherapy-based cure for PCa at any stage. As I wrote in an earlier blog, a major obstacle to discovering an effective PCa immunotherapy is the nature of the disease itself. PCa has built-in strategies to evade the body’s immune system, so scientists are exploring more than one pathway to empower the body’s own defenses more effectively.

Here are the two main categories of immunotherapies that are in clinical trials:

1. Vaccine therapies – Provenge falls into this category. It uses dendritic cells, a component of the immune system, to stimulate the immune system’s killer T-cells to tackle PCa cells. The dendritic cells are harvested from the patient’s own blood, then sent to a lab where they are “loaded” with information about the patient’s PCa cells. When injected back into the patient, they empower “killer” T-cells with this information. The T-cells then seek and destroy the cancer. There are two other vaccines of note: PSA-TRICOM and GVAX. “PSA-TRICOM uses viral vectors (vaccinia and fowlpox) in a prime-boost strategy, whereas GVAX is composed of 2 irradiated allogeneic prostate cancer cell lines (LNCaP and PC-3), which constitutively express granulocyte macrophage colony- stimulating factor.”^[ii]
2. Immune checkpoint inhibitors (ICIs) – Immune checkpoints are like cancer cells’ shield against killer T-cells. The cancer cells depend on mechanisms that switch on the checkpoints. Scientists are working on drugs that block, or inhibit, the ability of the cells to flip the “on switch”, so these drugs are called immune checkpoint inhibitors. This class of drugs has shown effectiveness against certain types of tumor and blood cancers, but so far clinical trial results have not been robust. At this time, the only FDA-approved ICI for prostate cancer is pembrolizumab (Keytruda).

It appears to help control the minority of PCa cells that have a specific genomic mutation, so it doesn’t have wide application. To broaden the number of PCa cell lines against which Keytruda might work, studies are done to combine it with various PCa chemotherapeutic drugs (combination therapy). While these trials have demonstrated some increase in the number of patients who respond, side effects can be awful. It will likely take years of exploring various combinations at different doses before we’ll know if ICIs will work against PCa.

In addition, other immunotherapeutic approaches that would engage T-cells with cancer cells are being explored. They are based on successes observed with blood cancers. However, the ability of tumor cancers like PCa to dodge or suppress the actions of the immune system has so far foiled these efforts. As of this writing, there is no PCa immunotherapy that offers broad effectiveness.

One final note: an interdisciplinary team out of Radboud University (Nijmegen, The Netherlands) is looking at innovative ways to integrate tumor ablation (destroying a tumor in the body) with biochemical agents that boost the body’s own immune response.^[iii] When a tumor is ablated (e.g., cryotherapy, HIFU, Focal Laser Ablation) the cancer cells that are destroyed leave behind debris, including surface proteins (antigens) that are like ID tags. The immune system naturally detects these antigens, which helps program T-cells. However, their anti-tumor activity usually needs a boost. This can come in the form of immunotherapeutic drugs administered directly into the ablation site, avoiding the kinds of harsh side effects seen with systemic immunotherapies in combination with chemotherapies.

There is no doubt that cancer is clever at camouflaging or shielding itself from the body’s defenses. It is reassuring to know that medical science is committed to outsmarting PCa. At the present time, the focus of research is conquering metastatic PCa, which has already survived surgery, radiation, androgen deprivation therapy, and chemotherapy. Undoubtedly, as success increases, the principles used in overcoming terminal PCa will be applied to localized early-stage PCa that is currently amenable to local treatment. It will be a great day when a newly diagnosed patient can take a pill or get a shot—and be cured of his disease!

NOTE: This content is solely for purposes of information and does not substitute for diagnostic or medical advice. Talk to your doctor if you are experiencing pelvic pain, or have any other health concerns or questions of a personal medical nature.

References

[i] Cercek A, Dos Santos Fernandes G, Roxburgh CS, Ganesh K et al. Mismatch Repair-Deficient Rectal Cancer and Resistance to Neoadjuvant Chemotherapy. Clin Cancer Res. 2020 Jul 1;26(13):3271-3279.
[ii] Kosoff, D. “Immunotherapeutics Aim for Larger Role in Prostate Cancer.” June 9, 2022. https://www.onclive.com/view/immunotherapeutics-aim-for-larger-role-in-prostate-cancer
[iii] van den Bijgaart RJE, Schuurmans F, Fütterer JJ, Verheij M, Cornelissen LAM, Adema GJ. Immune Modulation Plus Tumor Ablation: Adjuvants and Antibodies to Prime and Boost Anti-Tumor Immunity In Situ. Front Immunol. 2021
Apr 14;12:617365.