CAR T/mRNA

[dentaltwin]

...and solid tumors:

statnews.com/2022/04/10/mrn...

[Javelin18]

It will be interesting to see if something similar is tried with prostate cancer. Part of what appeals to me with CAR -T is that it stays in your system and can possibly be reactivated with other immunotherapy approaches.

[dentaltwin in reply to Javelin18]

The vaccine is SUPPOSED to overcome the problems so far with CAR T and solid tumors. This to me looks at least as, or more promising:

pennmedicine.org/news/news-...

[Javelin18 in reply to dentaltwin]

That looks really promising. I have a hypothesis that immunotherapy in prostate cancer is suppressed by macrophages. Prostate cancer is considered a cold tumor due to low T-cell infiltration. However, up to 60 percent of the tumor microenvironment is made up of macrophages.

Macrophages are also integral to the action of osteoblasts and osteoclasts, which regulate calcium transfer into and out of bones. This makes me think that they are exploited by PCa in bone metastases.

The CAR-T trial at City of Hope wipes out immune cells to overcome immunosuppression before injecting the CAR -T cells. CAR -M looks like a more direct route.

[dentaltwin in reply to Javelin18]

I've tried to get at least a basic understanding of immunology, but as you know it's incredibly complex and the knowledge base changes rapidly (and my last formal pathology and histology classes were almost 50 years ago) so I couldn't tell you about the influence of macrophages on lymphocyte function.

[Javelin18 in reply to dentaltwin]

Yes, it incredibly complex, and poorly understood. The research community is doing basic research during trials to try to understand effects, by doing whole genome sequencing of biopsy samples before and after treatment. I called my thoughts a hypothesis, but maybe more of a Scientific Wild A** Guess ( SWAG). I keep pinging researchers to see where their thoughts lie.

[dentaltwin in reply to Javelin18]

They're also doing sequencing of both somatic and germ-line mutations of tumors looking for "actionable targets" for "targeted therapy". As I found out during the course of my late wife's treatment for NSCLC, not all mutations are "actionable", and AFAIK all of these therapies fail eventually.

[Javelin18 in reply to dentaltwin]

The Metastatic Prostate Cancer Project mpcproject.org/home did a recent data release. There were around 50 individual mutations that occurred in just one patient in the survey population

[dentaltwin in reply to Javelin18]

Sure--and there can be multiple different types of mutations in a single gene. What you'll hear in all the ads for the immune checkpoint inhibitors used in lung cancer (nivolumab, pembrolizumab, ipilimubab etc. etc.) is that they are to be used only in cancers that are NOT EGFR mutated (presumably because the targeted therapies have a better chance of working). But the targeted therapies are more specific than that; one may be active against deletions of a specific gene on exon 19, while another may be active against a specific substitution on exon 21. If you have a different EGFR mutation you're SOL as far as the targeted therapies are concerned. So they either have to get therapies that target a far broader range of specific mutations, or they have to get better with the immunotherapies. (I suspect the immunotherapies may eventually have far broader applications, but though I've read quite a lot in the past 6 years I admit I'm way out of my depth here).

[Javelin18 in reply to dentaltwin]

Here's a paper discussing the first two patients. It talks about tolerability, and presence of the CAR-M cells following treatment, but no indication of efficacy.

jitc.bmj.com/content/9/Supp...

As I was guessing, they don't use chemotherapy to wipe out immune cells prior to injecting the CAR-M cells.

[Scout4answers in reply to dentaltwin]

CAR M looks very promising

[CAMPSOUPS]

Thank you to you and Javelin for a good discussion expanding on your post.