Thursday, October 30, 2014

CD40 Antibody therapy for melanoma....another way to activate the immune system?

CD40 is a positive signaling molecule (a co-stimulatory protein found on antigen presenting cells). It turns T-cells on.  It does not "take off the brakes" like anti-PD1 does, rather it "turns on the gas" to the immune system.  It appears that in this particular patient...after administration....the cancer was gone and a new set of T-cells developed.

Immune activation and a 9-year ongoing complete remission following CD40 antibody therapy and metastaectomy in a patient with metastatic melanoma.
Bajor, Torigian, Mick, et al.  Cancer Discov. 2014 Sep 24.

Direct immune activation via agonistic monoclonal antibodies is a potentially complimentary approach to therapeutic blockade of inhibitory immune receptors in cancer. Patient with metastatic melanoma was given an agonistic CD40 monoclonal antibody, underwent removal of a  single met and achieved a complete remission ongoing for more than 9 years after starting therapy.  Tumor microenvironment after immunotherapy was associated with  pro-inflammatory modulation and emergence of a de novo T-cell repertoire as detected by next-generation sequencing of T cell receptors in tumor and blood.  The de-novo T cell repertoire identified in the post-treatment met sample was also present - and in some cases expanded - in the circulation years after completion of therapy.

There is a fair amount of info lacking in this report.  How was CD40 administered? (I assume IV.)  For how long?  How often?  Side effects?  The implication (though not stated) is that only one met was removed and perhaps others resolved spontaneously due to the now stimulated immune system...though that is unclear.  However, I thought the process was interesting and perhaps more info and studies in this direction will occur in the future.

Yours, c

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