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Landmark study for Cobbold on novel tumour antigens

Article Date: 19.09.13
Category: Science stories

Dr Mark Cobbold has published a key study on a novel set of tumour antigens in the journal Science Translational Medicine.

The study, conducted with a host of collaborators both in Birmingham and in the University of Virginia, USA, focusses on  naturally processed peptide antigens that incorporate phosphate groups and are presented by Major Histocompatibility Complex proteins.

The source antigens for these peptides are phosphoproteins that are degraded by the antigen processing machinery before presentation at the cell surface.

As kinase pathways that generate such phosphoprotein antigens are known to be strongly dysregulated in cancer, presentation of these peptides could provide an “immunological signature of transformed self” for recognition by T cells.

Mark explained the key advances made in the study:  “Firstly, we discovered 95 new phosphorylated tumour antigens. Secondly, we found that whereas healthy individuals typically have immune responses against many of these antigens,  in contrast, patients with leukaemias (both AML and CLL), often lack responses against them. Also,  patients with stronger responses against the antigens had a better prognosis, and importantly, responses were restored following a stem cell (or bone marrow) transplant .”

The study also raises key questions, as well as highlighting therapeutic relevance.

“We do not know if the responses in patients with leukaemia were lost prior or after the development of leukaemia, or whether they never generated in the first place.” commented Mark.

“However, the increased immunity to them after stem cell transplantation may help explain why this treatment is able to cure patients with leukaemia.”

In the relatively young field of phosphopeptide immunology, there is clearly much work yet to do, however Mark stressed the clinical potential of these antigens: “This study  is our first attempt to understand how immune responses to phosphorylated antigens are controlled – both in health and in cancer patients. There are many questions left  to answer, however these early results suggest the ability to recognise these antigens may well be important in targeting cancer,  and we would definitely consider incorporating them as a part of novel cancer vaccines in the future.”

Sci Transl Med. 2013 Sep 18;5(203):203ra125.

MHC class I-associated phosphopeptides are the targets of memory-like immunity in leukemia
Cobbold M, De La Peña H, Norris A, Polefrone JM, Qian J, English AM, Cummings KL, Penny S, Turner JE, Cottine J, Abelin JG, Malaker SA, Zarling AL, Huang HW,Goodyear O, Freeman SD, Shabanowitz J, Pratt G, Craddock C, Williams ME, Hunt DF, Engelhard VH.

Follow Mark on Twitter: @Mark_Cobbold