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Julie Bonigen, Christine Raynaud-Donzel, José Hureaux, Nora Kramkimel, Astrid Blom, Géraldine Jeudy, Anne-Laure Breton, Thomas Hubiche, Christophe Bedane, Delphine Legoupil, Anne Pham-Ledard, Julie Charles, Maurice Pérol, Emilie Gérard, Patrick Combemale, Daphné Bonnet, Michèle-Léa Sigal, Emmanuel Mahé
Nivolumab (Opdivo(®) ), pembrolizumab (Keytruda(®) ), atezolizumab, and pidilizumabab are anti-PD1 monoclonal antibodies. Nivolumab is licensed in advanced melanoma and second-line therapy of advanced or metastatic non-small cell lung cancer. When activated, the programmed cell death (PD)-1 is implicated in the inhibition of the immune system. Anti-PD1 removes this inhibition and allows the immune system to control tumour cell progression.(1-4) Immune-mediated toxicity of this treatment have been reported, either organ-specific toxicities - i...
October 14, 2016: Journal of the European Academy of Dermatology and Venereology: JEADV
Gerry Kwok, Thomas C C Yau, Joanne W Chiu, Eric Tse, Yok-Lam Kwong
The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies...
July 11, 2016: Human Vaccines & Immunotherapeutics
C Granier, S Karaki, H Roussel, C Badoual, T Tran, M Anson, E Fabre, S Oudard, E Tartour
Cancer immunotherapy has occupied a marginal therapeutic option in cancer despite strong arguments documenting the role of the immune system in controlling the proliferation of cancers. The recent success of immunotherapy results from a change in the past paradigm. From now on, the goal is not only to activate the immune system against tumor, but also to take account of the immunosuppressive tumor microenvironment Among these mechanisms, negative costimulatory molecules (CTLA-4, PD-1, etc.) expressed by T cells in the tumor could explain their lack of effectiveness in inhibiting tumor growth...
June 28, 2016: La Revue de Médecine Interne
Carmel L Mercado, Brian C Toy, Henry B Kistler, Darius M Moshfeghi
A 92-year-old man presented with months of progressive blurry vision, worsening acutely in his right eye. He denied pain, diplopia, or photopsias. His history was significant for multiple myeloma, prostate cancer, and malignant melanoma of his right shoulder treated with local excision. He had local recurrence with hepatic metastasis of the melanoma treated with radiation and chemotherapy. On examination, his visual acuity was counting fingers in the right eye and 20/60 in the left eye. Amsler grid testing demonstrated metamorphopsia in the right eye...
May 1, 2016: Ophthalmic Surgery, Lasers & Imaging Retina
Adil Daud, Prachi Nandoskar
No abstract text is available yet for this article.
June 2016: Expert Opinion on Drug Safety
Emma D Deeks
Pembrolizumab (Keytruda(®)) is a humanized monoclonal antibody against programmed death receptor-1 (PD-1), a key immunoinhibitory checkpoint protein implicated in down-regulating anti-tumour immune responses. This intravenous drug is indicated for the treatment of advanced (unresectable or metastatic) melanoma, on the basis of its clinical benefit in this setting in the phase I KEYNOTE 001 trial (expansion cohorts) and the phase II and III trials, KEYNOTE 002 and 006. These studies were conducted in ipilimumab-naïve and/or ipilimumab-experienced patients and assessed varying pembrolizumab regimens administered every 2 or 3 weeks, all of which helped to determine the recommended dosage of 2 mg/kg every 3 weeks...
March 2016: Drugs
Jonathan L Messerschmidt, George C Prendergast, Gerald L Messerschmidt
UNLABELLED: With the Food and Drug Administration and other worldwide regulatory authorities' approval of ipilimumab (Yervoy), sipuleucel-T (Provenge), nivolumab (Opdivo), and pembrolizumab (Keytruda), oncologic therapy has now moved into noncancer cell targets within the immune system. For many nonimmunologists, understanding how these vastly different therapies work to improve survival, like no other therapies have in the past, is a challenge. The present report reviews the normal function of the immune system, how cancers escape the normal immune system, and how these new therapies improve immune system reactions against cancers...
February 2016: Oncologist
Safiya Karim, Natasha Leighl
New insights into the interaction between the immune system and the tumor microenvironment have led to the development of checkpoint inhibitors that target the PD-1/PD-L1 pathway. Pembrolizumab (MK-3475, lambrolizumab, Keytruda(®)) is a PD-1 inhibitor that has shown clinical activity in a variety of solid tumors and is currently approved for the second-line treatment of PD-L1-positive non-small-cell lung cancer and for unresectable/metastatic melanoma. This article will discuss the results of early-phase trials of pembrolizumab in thoracic malignancies as well as ongoing studies aimed to confirm clinical benefit...
January 2016: Future Oncology
Lisa A Raedler
No abstract text is available yet for this article.
March 2015: American Health & Drug Benefits
Xiaoyu Yang, Fengqiang Wang, Ying Zhang, Larry Wang, Svetlana Antonenko, Shuli Zhang, Yi Wei Zhang, Mohammad Tabrizifard, Grigori Ermakov, Derek Wiswell, Maribel Beaumont, Liming Liu, Daisy Richardson, Mohammed Shameem, Alexandre Ambrogelly
IgG4 antibodies are evolving as an important class of cancer immunotherapies. However, human IgG4 can undergo Fab arm (half molecule) exchange with other IgG4 molecules in vivo. The hinge modification by a point mutation (S228P) prevents half molecule exchange of IgG4. However, the experimental confirmation is still expected by regulatory agencies. Here, we report for the first time the extensive analysis of half molecule exchange for a hinge-modified therapeutic IgG4 molecule, pembrolizumab (Keytruda) targeting programmed death 1 (PD1) receptor that was approved for advanced melanoma...
December 2015: Journal of Pharmaceutical Sciences
(no author information available yet)
No abstract text is available yet for this article.
May 2015: Nature Biotechnology
(no author information available yet)
No abstract text is available yet for this article.
November 10, 2014: Medical Letter on Drugs and Therapeutics
Kunj Gohil
Naltrexone/bupropion (Contrave) for weight management; pembrolizumab (Keytruda) for melanoma; dolutegravir/abacavir/lamivudine (Triumeq) for HIV-1; and immune globulin infusion 10% (human) with recombinant human hyaluronidase (Hyqvia) for primary immunodeficiency.
November 2014: P & T: a Peer-reviewed Journal for Formulary Management
Raewyn M Poole
Pembrolizumab [Keytruda(®) (US)], a humanized monoclonal antibody against the programmed death receptor-1 (PD-1) protein, has been developed by Merck & Co for the treatment of cancer. Pembrolizumab has received its first global approval for the treatment of advanced, unresectable or metastatic malignant melanoma in the US, for use in patients with disease progression after prior treatment with ipilimumab and, for BRAF V600 mutation-positive patients, a BRAF inhibitor. It is the first anti-PD-1 therapy to receive regulatory approval in the US, and is currently under regulatory review in the EU...
October 2014: Drugs
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