12:00 AM
Oct 25, 2012
 |  BC Innovations  |  Cover Story

Melanoma's hidden act

Researchers at the University of Bonn and the Johannes Gutenberg University Mainz have shown that melanoma cells can acquire resistance to adoptive T cell transfer therapies by dedifferentiating themselves to hide antigens.1 The group now is trying to circumvent this resistance mechanism and thinks doing so could improve treatment responses for current T cell therapy protocols.

Adoptive T cell transfer is one of three immunotherapy-based strategies used to treat metastatic melanomas and typically is used in patients for whom standard treatments have failed.

The two other immunotherapy approaches being developed

for melanoma involve nonspecific immunostimulation and active immunization.

The two marketed immunotherapies for melanoma work via nonspecific immunostimulation: Proleukin aldesleukin IL-2 from Novartis AG and Yervoy ipilimumab, a human mAb against CTLA-4 (CD152) receptor from Bristol-Myers Squibb Co. Both drugs cause tumor regression in up to 15% of patients.2,3

The two most advanced active immunizers for melanoma are talimogene laherparepvec from Amgen Inc. and GSK1572932A from GlaxoSmithKline plc. Talimogene laherparepvec is a modified herpes simplex virus type 1 (HSV-1) encoding granulocyte macrophage colony-stimulating factor (GM-CSF; CSF2). GSK1572932A is a vaccine against melanoma-associated antigen A3 (MAGEA3). Both compounds are in Phase III testing.

Adoptive cell transfer typically involves isolating, expanding and activating tumor-infiltrating lymphocytes or peripheral blood T cells and then infusing the cells back into the patient.

Although peripheral blood T cells are more plentiful and are easier to isolate than tumor-infiltrating lymphocytes, they lack tumor specificity and thus need to be engineered to express T cell receptors (TCRs) or chimeric antigen receptors that target tumor antigens before they are infused back into the patient.

Companies have avoided adoptive cell therapies because they need to be tailored to each patient. Clinical trials evaluating adoptive cell therapies are being run by research...

Read the full 1540 word article

User Sign in

Trial Subscription

Get a 4-week free trial subscription to BioCentury Innovations

Article Purchase

$85 USD
More Info >