antibody targeting PD-1 to modulate immune response

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CT-011, a Humanized Antibody Interacting with PD-1, in Patients with

Advanced Hematologic Malignancies

Snips from technical full paper: http://bit.ly/a3lHUc

CT-011 is a humanized antibody that modulates the immune response.

One of the leading causes for immune suppression in cancer patients was

suggested to be associated with the elevated expression of PD-L1 (B7-H1) at

tumor-involved sites, resulting in local suppression and apoptosis of

tumor-infiltrating effector lymphocytes.

Recent clinical data support notion of PD-L1 (B7-H1) playing an important

role in immune evasion of tumor cells (9

<http://clincancerres.aacrjournals.org/content/14/10/3044.full#ref-9> ).

Thus, we hypothesized that targeting B7-H1/PD-1 interactions and,

specifically, interference with the function of PD-1 by mAbs may potentially

be useful in enhancing immunity against cancer antigens.

Interaction of CT-011 with PD-1, a protein belonging to the B7 receptor

family present on lymphocytes, leads to stimulation of natural killer cell

activity and to extended survival of effector/memory T cells, culminating in

the enhancement of antitumor immune response and the generation of

tumor-specific memory cells (6

<http://clincancerres.aacrjournals.org/content/14/10/3044.full#ref-6> -8

<http://clincancerres.aacrjournals.org/content/14/10/3044.full#ref-8> ).

These characteristics advocate the application of CT-011 to a wide variety

of tumors, independent of the oncogenic source of disease. In addition,

CT-011 can potentially be combined with a range of therapies including

various vaccines, adoptive immunotherapy including donor lymphocyte

infusions, stem cell transplantation, and ex vivo stimulation of

tumor-specific immune cells.

Accumulating experimental evidence indicates that PD1 is a co-inhibitor and

primarily involved in the regulation of T-cell and natural killer cell

responses.

The study showed the antibody to be safe and well tolerated in this patient

population. No single maximum tolerated dose was defined in this study.

Clinical benefit was observed in 33% of the patients with one complete

remission. Pharmacokinetic analyses show that serum Cmax and the AUC of

CT-011 increased proportionally with dose. The median t1/2 of CT-011 ranged

from 217 to 410 hours. Sustained elevation in the percentage of peripheral

blood CD4+ lymphocytes was observed up to 21 days following CT-011

treatment.

See Clinical Studies recruiting patients - so far, combining CT-011 with

Rituxan http://bit.ly/1Bj7r1

So far for follicular (recruiting) and DLBCL (active but not recruiting)

All the best,

~ Karl

Patients Against Lymphoma

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