Consultation with DrAparicio MD Anderson

[Javelin18]

I met with Dr Aparicio on Wednesday to talk about my treatment options further down the road, discuss my idea of using something similar to convalescent plasma and try to learn more about immunotherapy. A member asked me to post what I learned, this is the first of a few posts

I’m not a doctor, but I play one on TV. I’ve learned enough to ask good questions, but not enough to understand all the answers. I’ve got a bit of research to do before I understandv enough to create as meaningful post on the broader topics. Right now I want to talk about my idea of convalescent plasma.

There have been some trials of taking T cells from parents with durable responses, and injecting them in patients with active disease. They have found some benefit from technique, but the T cells are foreign and have a limited life. The injection works better if the patient has depleted T cells after chemotherapy, as the body doesn’t reject them as readily. However, immunity isn’t transferred from T cell to T cell.

Naive T cells are trained by contact with dendritic cells that express the cancer antigens. Some of the cells are active and some T memory cells remain dormant, creating long term immunity. Once a patient is in long term remission, the antigens are no longer present and dendritic cells won’t present the antigen.

Sipeleucel T and APCEDEN are dendritic vaccines the remove a patient’s dendritic cells, and train them with one (or possibly more with APCEDEN) cancer antigen then reinject them. The dendritic cells then come in contact with naive T cells and train them to recognize the cancer.

Both vaccines have had limited success, but haven’t yielded broad based cures. My thought is that the cancer and immune system are too complex to use a small number of antigens successfully. Given that complexity, I had the idea that patients with spontaneous remission might have immune systems that have figured out how to recognize and kill cancer cells. It was my hope that the immunity could be transferred to other patients.

After some research I thought that trained T cells could be killed, and the antigens they released could train a new patient’s dendritic cells to create a more effective vaccine. Dr Aparicio said she hadn’t heard of any cases of spontaneous remission in prostate cancer. She also pointed out that the cancer would likely be different from patient to patient, so an immune cure in one patient might not be effective in another patient.

I think I will give this idea a rest, while I learn more about the immune system. She did tell me that a patient’s T cells could be tested for immunogenic activity by seeing if they release cytokines when exposed to cancer cells in vitro.

[Tall_Allen]

Sadly most prostate cancers are immunologically cold. Cytokines and chemokines can be pro-inflammatory (eliciting an immune response) and antiinflammatory (dampening an immune response). Immune infiltration is poor, and immunosuppressive macrophages,Tregs, tumor neutrophils, and myeloid-derived suppressor cells are common. Also, it creates an immunosuppressive microenvironment, especially in bone. The immune system seems to be active in promoting progression. Lots to overcome.

[Javelin18 in reply to Tall_Allen]

Well said. Definitely a lot to overcome, and an adaptive complex system. I was a bit despairing of how long it would take researchers to figure out how to master that complexity, but Dr Aparicio was hopeful.

[Tall_Allen in reply to Javelin18]

I think immunotherapy has a place in combination of therapies (as with radiotherapy or chemotherapy) for PCa, but I despair of any monotherapeutic approach. The antibody/drug conjugates haven't worked so far, but I'm still hopeful about the BiTEs and maybe the two CAR-T drugs.

[Schwah in reply to Tall_Allen]

What do you mean by “. The immune system seems to be active in promoting progression.”

[Tall_Allen in reply to Schwah]

Just that. The immune system isn't necessary our friend when it comes to PCa progression. Certain parts promote tumor progression.

[Javelin18]

I saw your post. Great summary.

Dr Aparicio gave me a broad overview of immune therapy, including BITE, CAR T, checkpoint inhibitors and vaccines. I’m still trying to integrate the information into a concise post, but have some learning to do before that.