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New directions in immunosuppression after he... [Nat Rev Cardiol. 2013] - PubMed - NCBI

PubMed comprises more than 23 million citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.
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heart transplantation

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Immunology and Biotherapies
Page Ressources et Actualités du DIU immunologie et biothérapies
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Resources for DIU Immunologie et Biothérapies

DIU Immunologie et Biotherapies is a french diploma associating many french universities and immunology laboratories. It is dedicated to the involvement of immunology in new biotherapies, either molecular or cellular

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Development and characterization of broadly cross-reactive monoclonal antibodies against all known Ebolavirus species

Development and characterization of broadly cross-reactive monoclonal antibodies against all known Ebolavirus species | Immunology and Biotherapies | Scoop.it
Infectious Disease Article: Development and characterization of broadly cross-reactive monoclonal antibodies against all known Ebolavirus species
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Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma - Cancer Letters

Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinoma - Cancer Letters | Immunology and Biotherapies | Scoop.it

Highlights

 

First time demonstrating that CD47 blockade has anti-tumor effects against HCC.

In vitro CD47 blockade results in increase in phagocytosis of HCC cells.

In vivo CD47 blockade inhibits HCC tumor growth in hetero/orthotopic models.

CD47mAb400 is clearly more efficacious than widely-investigated B6H12 antibody.

 

Abstract

Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival times. The efficacy of current systemic therapies for HCC is limited. In this study, we used xenograft tumor models to investigate the use of antibodies that block CD47 and inhibit HCC tumor growth. Immunostaining of tumor tissue and HCC cell lines demonstrated CD47 over-expression in HCC as compared to normal hepatocytes. Macrophage phagocytosis of HCC cells was increased after treatment with CD47 antibodies (CD47mAbs) that block CD47 binding to SIRPα. Further, CD47 blockade inhibited tumor growth in both heterotopic and orthotopic models of HCC, and promoted the migration of macrophages into the tumor mass. Our results demonstrate that targeting CD47 by specific antibodies has potential immunotherapeutic efficacy in human HCC.


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Krishan Maggon 's curator insight, May 26, 1:45 AM

Cancer Letters

Volume 360, Issue 2, 1 May 2015, Pages 302–309

Original Articles Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinomaZhenyu Xiaoa, 1, Haniee Chunga, 1, Babak Banana, Pamela T. Manningb, Katherine C. Otta, Shin Linc,Benjamin J. Capocciaa, Vijay Subramaniana, Ronald R. Hiebschb, Gundumi A. Upadhyaa, Thalachallour Mohanakumara, e, William A. Frazierd, Yiing Lina, , , William C. Chapmana, ,    doi:10.1016/j.canlet.2015.02.036

Krishan Maggon 's curator insight, May 26, 1:48 AM
Cancer Letters

Volume 360, Issue 2, 1 May 2015, Pages 302–309

Original Articles Antibody mediated therapy targeting CD47 inhibits tumor progression of hepatocellular carcinomaZhenyu Xiaoa, 1, Haniee Chunga, 1, Babak Banana, Pamela T. Manningb, Katherine C. Otta, Shin Linc,Benjamin J. Capocciaa, Vijay Subramaniana, Ronald R. Hiebschb, Gundumi A. Upadhyaa, Thalachallour Mohanakumara, e, William A. Frazierd, Yiing Lina, , , William C. Chapmana, ,    doi:10.1016/j.canlet.2015.02.036
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European Medicines Agency - News and Events - Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 May 2015

European Medicines Agency - News and Events - Meeting highlights from the Committee for Medicinal Products for Human Use (CHMP) 18-21 May 2015 | Immunology and Biotherapies | Scoop.it
European Union agency responsible for the protection of public and animal health through the scientific evaluation and supervision of medicines.

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Krishan Maggon 's curator insight, May 22, 8:53 AM

Two generic medicines received positive opinions from the CHMP: Bortezomib Accord(bortezomib) for the treatment of multiple myeloma and mantle cell lymphoma andPregabalin Zentiva (pregabalin) for the treatment of epilepsy and generalised anxiety disorder.

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Antibody-Drug Conjugates: Design, Formulation and Physicochemical Stability - Online First - Springer

Antibody-Drug Conjugates: Design, Formulation and Physicochemical Stability - Online First - Springer | Immunology and Biotherapies | Scoop.it
Abstract

The convergence of advanced understanding of biology with chemistry has led to a resurgence in the development of antibody-drug conjugates (ADCs), especially with two recent product approvals. Design and development of ADCs requires the synergistic combination of the monoclonal antibody, the linker and the payload. Advances in antibody science has enabled identification and generation of high affinity, highly selective, humanized or human antibodies for a given target. Novel linker technologies have been synthesized and highly potent cytotoxic drug payloads have been created. As the first generation of ADCs utilizing lysine and cysteine chemistries moves through the clinic and into commercialization, second generation ADCs involving site specific conjugation technologies are being evaluated and tested. The latter aim to be better characterized and controlled, with wider therapeutic indices as well as improved pharmacokinetic-pharmacodynamic (PK-PD) profiles. ADCs offer some interesting physicochemical properties, due to conjugation itself, and to the (often) hydrophobic payloads that must be considered during their CMC development. New analytical methodologies are required for the ADCs, supplementing those used for the antibody itself. Regulatory filings will be a combination of small molecule and biologics. The regulators have put forth some broad principles but this landscape is still evolving.


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Krishan Maggon 's curator insight, May 24, 1:57 AM
Pharmaceutical ResearchMay 2015Date: 19 May 2015Antibody-Drug Conjugates: Design, Formulation and Physicochemical StabilitySatish K. Singh, Donna L. Luisi, Roger H. Pak
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Monoclonal antibodies in acute lymphoblastic leukemia

Abstract

With modern intensive combination polychemotherapy, the complete response (CR) rate in adults with acute lymphoblastic leukemia (ALL) is 80-90%, and the cure rate 40-50%. Hence there is a need to develop effective salvage therapies and combine novel agents with standard effective chemotherapy. ALL leukemic cells express several surface antigens amenable to target therapies, including CD20, CD22, and CD19. Monoclonal antibodies target these leukemic surface antigens selectively, and minimize off-target toxicity. When added to frontline chemotherapy, rituximab, an antibody directed against CD20, increases cure rates of adults with Burkitt leukemia from 40% to 80%, and those with pre-B ALL from 35% to 50%. Inotuzumab ozogamicin, a CD22 monoclonal antibody bound to calicheamicin, has resulted in marrow CR rates of 55% and a median survival of 6-7 months when given to patients with refractory-relapsed ALL. Blinatumomab, a biallelic T-cell engaging CD3-CD19 monoclonal antibody, also resulted in overall response rates of 40-50% and a median survival of 6.5 months in a similar refractory-relapsed population. Other promising monoclonal antibodies targeting CD20 (ofatumumab, obinutuzumab), or CD19 or CD20 and bound to different cytotoxins or immunotoxins are under development. Combined modalities of chemotherapy and the novel monoclonal antibodies are under investigation.


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Krishan Maggon 's curator insight, May 24, 11:57 PM

Monoclonal antibodies in acute lymphoblastic leukemia

Elias Jabbour, Susan O'Brien, Farhad Ravandi, HagopKantarjianBlood Jan 2015, DOI: 10.1182/blood-2014-08-596403
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USP Publishes Monoclonal Antibody Guidelines - Compliance Team Inc

USP Publishes Monoclonal Antibody Guidelines - Compliance Team Inc | Immunology and Biotherapies | Scoop.it
As FDA gears up towards approving biosimilar drugs in the United States, it is unquestionable that the role of biologics has rapidly expanded in healthcare, raising questions and presenting crucial issues associated with their quality and efficacy.
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Overview | Cancer Immunology & Immunotherapy | Research Solutions | PerkinElmer

Overview | Cancer Immunology & Immunotherapy | Research Solutions | PerkinElmer | Immunology and Biotherapies | Scoop.it
Our Cancer Immunology & Immunotherapy Research Solutions include advanced staining methods, multispectral imaging systems, image analysis services, and contract services.
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Safety and activity of the anti-CD79B antibody–...

Safety and activity of the anti-CD79B antibody–... | Immunology and Biotherapies | Scoop.it
Safety and activity of the anti-CD79B antibody–drug conjugate polatuzumab vedotin in relapsed or refractory B-cell non-Hodgkin lymphoma and chronic lymphocytic leukaemia: a phase 1 study - The Lanc...
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Efficacy and safety of cord blood-derived cytokine-induced killer cells in treatment of patients with malignancies. - PubMed - NCBI

Efficacy and safety of cord blood-derived cytokine-induced killer cells in treatment of patients with malignancies. - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
Cytotherapy. 2015 May 9. pii: S1465-3249(15)00855-5. doi: 10.1016/j.jcyt.2015.04.002. [Epub ahead of print]
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Bertilimumab - Immune Pharmaceuticals

Bertilimumab is a fully human, IgG4-type monoclonal antibody (mAb) that blocks the activity of a protein called eotaxin-1 that plays an important role in inflammation in multiple clinical indications.

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Krishan Maggon 's curator insight, May 5, 4:31 AM

Immune Pharmaceuticals Inc., a clinical stage bio-pharmaceutical company with a monoclonal antibody, bertilimumab, for the treatment of auto-immune diseases, and STC Biologics, a biotechnology development company led by alumni of Genentech, Shire, Novartis and Merrimack Pharmaceuticals, announced today that they are entering into a strategic partnership to accelerate the development of NanomAbs, a new generation of Antibody Nanoparticle Conjugates allowing the targeted delivery of chemo-therapeutics.



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First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers

First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers | Immunology and Biotherapies | Scoop.it
(2014). First human study of a chimeric anti-methamphetamine monoclonal antibody in healthy volunteers. mAbs: Vol. 6, No. 6, pp. 1649-1656. doi: 10.4161/19420862.2014.976431
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Scooped by Gilbert Faure au nom de l'ASSIM from Melanoma BRAF Inhibitors Review
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Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patients

Abstract

Enhancing immune responses with immune-modulatory monoclonal antibodies directed to inhibitory immune receptors is a promising modality in cancer therapy. Clinical efficacy has been demonstrated with antibodies blocking inhibitory immune checkpoints such as cytotoxic T lymphocyte–associated antigen 4 (CTLA-4) or PD-1/PD-L1. Treatment with ipilimumab, a fully human CTLA-4–specific mAb, showed durable clinical efficacy in metastatic melanoma; its mechanism of action is, however, only partially understood. This is a study of 29 patients with advanced cutaneous melanoma treated with ipilimumab. We analyzed peripheral blood mononuclear cells (PBMCs) and matched melanoma metastases from 15 patients responding and 14 not responding to ipilimumab by multicolor flow cytometry, antibody-dependent cell-mediated cytotoxicity (ADCC) assay, and immunohistochemistry. PBMCs and matched tumor biopsies were collected 24 h before (i.e., baseline) and up to 4 wk after ipilimumab. Our findings show, to our knowledge for the first time, that ipilimumab can engage ex vivo FcγRIIIA (CD16)-expressing, nonclassical monocytes resulting in ADCC-mediated lysis of regulatory T cells (Tregs). In contrast, classical CD14++CD16−monocytes are unable to do so. Moreover, we show that patients responding to ipilimumab display significantly higher baseline peripheral frequencies of nonclassical monocytes compared with nonresponder patients. In the tumor microenvironment, responders have higher CD68+/CD163+ macrophage ratios at baseline and show decreased Treg infiltration after treatment. Together, our results suggest that anti–CTLA-4 therapy may target Tregs in vivo. Larger translational studies are, however, warranted to substantiate this mechanism of action of ipilimumab in patients.


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Krishan Maggon 's curator insight, May 10, 1:55 PM

PNAS

Emanuela Romano, doi: 10.1073/pnas.1417320112

 

Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patientsEmanuela Romanoa,b,c,1, Monika Kusio-Kobialkab, Periklis G. Foukasc,d, Petra Baumgaertnerc,Christiane Meyerc, Pierluigi Ballabenie, Olivier Michielina,c, Benjamin Weidef, Pedro Romeroc, andDaniel E. Speiserc

Author Affiliations

Edited by Ira Mellman, Genentech, Inc., South San Francisco, CA, and approved March 30, 2015 (received for review September 9, 2014)

Krishan Maggon 's curator insight, May 12, 3:05 AM

PNAS

Emanuela Romano, doi: 10.1073/pnas.1417320112

 

Ipilimumab-dependent cell-mediated cytotoxicity of regulatory T cells ex vivo by nonclassical monocytes in melanoma patientsEmanuela Romanoa,b,c,1, Monika Kusio-Kobialkab, Periklis G. Foukasc,d, Petra Baumgaertnerc,Christiane Meyerc, Pierluigi Ballabenie, Olivier Michielina,c, Benjamin Weidef, Pedro Romeroc, andDaniel E. Speiserc

Author Affiliations

Edited by Ira Mellman, Genentech, Inc., South San Francisco, CA, and approved March 30, 2015 (received for review September 9, 2014)

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When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy | Read by QxMD

When blood transfusion medicine becomes complicated due to interference by monoclonal antibody therapy | Read by QxMD | Immunology and Biotherapies | Scoop.it
Great article: When blood transfusion medicine becomes complicated due to interference by monoclonal a... http://t.co/8LkEpj47Wo #ReadByQxMD
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Frontiers | Utilizing Chimeric Antigen Receptors to Direct Natural Killer Cell Activity | NK Cell Biology

Natural killer (NK) cells represent an attractive lymphocyte population for cancer immunotherapy due to their ability to lyse tumor targets without prior sensitization and without need for HLA-matc...
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Scooped by Gilbert Faure au nom de l'ASSIM from PARP Inhibitors Cancer Review
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Action and resistance of monoclonal CD20 antibodies therapy in B-cell non-hodgkin lymphomas - Cancer Treatment Reviews

Highlights

 

Anti-CD20 mAbs combined with chemotherapy have become the standard treatment of Non-Hodgkin Lymphomas (NHL).

Mechanisms of action of this anti-CD20 mAbs in vivo are not fully understood.

Binding of rituximab to CD20 is not sufficient to heal every patient with a Non-Hodgkin Lymphoma.

We review the mechanisms of action and resistance of rituximab, and the efforts needed to overcome it.

We also focus on new drugs targeting pathways implicated in resistance to anti-CD20 mAbs.

 

Abstract

Anti-CD20 monoclonal antibodies (mAbs) have improved patient’s survival with non-Hodgkin lymphoma, when combined with chemotherapy. Several mechanisms of action have been reported, including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity and induction of apoptosis. Despite the large amount of studies and published data, the role each mechanism played in vivo is not fully understood. Furthermore, the reason why a significant percentage of patients are refractory or resistant remains unknown. Several activated intracellular signaling pathways have been implicated in the mechanisms of resistance of rituximab. In the present manuscript, we review those mechanisms and new anti-CD20 mAbs, as well as the efforts being accomplished to overcome it, focusing on new drugs targeting pathways implicated in resistance to rituximab.


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Krishan Maggon 's curator insight, May 26, 1:53 AM
Cancer Treatment Reviews

Available online 19 May 2015

In Press, Accepted Manuscript — Note to users

 Action and resistance of monoclonal CD20 antibodies therapy in B-cell non-hodgkin lymphomasD. Pérez-Callejo , J. González-Rincón , A. Sánchez , M. Provencio , M. Sánchez-Beato,   doi:10.1016/j.ctrv.2015.05.007
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New biotechnology for high efficiency purification of live human cells

Cell therapies require a purification step that isolates the desired cell types from contaminating cells.
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Visterra collaborates with A*STAR to make monoclonal antibody for dengue | Vaccine News

Visterra Inc., a clinical-stage biotechnology company with a unique technology platform to discover disease targets and create novel treatments for infectious diseases, and the Agency for Science, Technology and Research’s (A*STAR) Drug Discovery...
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Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab. - PubMed - NCBI

Colitis mimicking graft-versus-host disease during treatment with the anti-CCR4 monoclonal antibody, mogamulizumab. - PubMed - NCBI | Immunology and Biotherapies | Scoop.it
Int J Hematol. 2015 May 21. [Epub ahead of print]
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Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas, Leukemia & Lymphoma, Informa Healthcare

Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas, Leukemia & Lymphoma, Informa Healthcare | Immunology and Biotherapies | Scoop.it
Phase I Study of the Anti-CD74 Monoclonal Antibody hLL1 in Patients with Previously Treated B-Cell Lymphomas http://t.co/ko87Y6QC2y
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Krishan Maggon 's curator insight, May 25, 5:56 AM

No objective response observed in Phase I trial

 

 

Leukemia & Lymphoma

 

ORIGINAL ARTICLE: RESEARCH

Phase I study of the anti-CD74 monoclonal antibody milatuzumab (hLL1) in patients with previously treated B-cell lymphomas

 

Posted online on May 12, 2015. (doi:10.3109/10428194.2015.1028052)




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Clinical improvement in psoriasis with specific targeting of interleukin-23

Abstract

 

Psoriasis is a chronic inflammatory skin disorder that affects approximately 2–3% of the population worldwide and has severe effects on patients’ physical and psychological well-being1, 2, 3. The discovery that psoriasis is an immune-mediated disease has led to more targeted, effective therapies; recent advances have focused on the interleukin (IL)-12/23p40 subunit shared by IL-12 and IL-23. Evidence suggests that specific inhibition of IL-23 would result in improvement in psoriasis. Here we evaluate tildrakizumab, a monoclonal antibody that targets the IL-23p19 subunit, in a three-part, randomized, placebo-controlled, sequential, rising multiple-dose phase I study in patients with moderate-to-severe psoriasis to provide clinical proof that specific targeting of IL-23p19 results in symptomatic improvement of disease severity in human subjects. A 75% reduction in the psoriasis area and severity index (PASI) score (PASI75) was achieved by all subjects in parts 1 and 3 (pooled) in the 3 and 10 mg kg−1 groups by day 196. In part 2, 10 out of 15 subjects in the 3 mg kg−1 group and 13 out of 14 subjects in the 10 mg kg−1 group achieved a PASI75 by day 112. Tildrakizumab demonstrated important clinical improvement in moderate-to-severe psoriasis patients as demonstrated by improvements in PASI scores and histological samples.


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Krishan Maggon 's curator insight, May 14, 3:07 AM

NATURE | LETTER

Clinical improvement in psoriasis with specific targeting of interleukin-23Tamara Kopp,Elisabeth Riedl,Christine Bangert,Edward P. Bowman,Elli Greisenegger,Ann Horowitz,Harald Kittler,Wendy M. Blumenschein,Terrill K. McClanahan,Thomas Marbury,Claus Zachariae,Danlin Xu,Xiaoli Shirley Hou,Anish Mehta,Anthe S. Zandvliet,Diana Montgomery,Frank van Aarle& Sauzanne KhaliliehAffiliationsContributionsCorresponding authorNature 521, 222–226 (14 May 2015) doi:10.1038/nature14175Received 23 December 2013 Accepted 23 December 2014 Published online 09 March 2015Corrected online 13 May 2015
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Frontiers | Revving up Natural Killer Cells and Cytokine-Induced Killer Cells Against Hematological Malignancies | NK Cell Biology

Natural killer (NK) cells belong to innate immunity and exhibit cytolytic activity against infectious pathogens and tumor cells. NK-cell function is finely tuned by receptors that transduce inhibit...
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The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in Melanoma

Findings

The anti-PD-1 and anti-PD-L1 agents have been reported to have impressive antitumor effects in several malignancies, including melanoma. The greatest clinical activity in unselected patients has been seen in melanoma. Tumor expression of PD-L1 is a suggestive, but inadequate, biomarker predictive of response to immune-checkpoint blockade. However, tumors expressing little or no PD-L1 are less likely to respond to PD-1 pathway blockade. Combination checkpoint blockade with PD-1 plus cytotoxic T-lymphocyte antigen (CTLA)-4 blockade appears to improve response rates in patients who are less likely to respond to single-checkpoint blockade. Toxicity with PD-1 blocking agents is less than the toxicity with previous immunotherapies (eg, interleukin 2, CTLA-4 blockade). Certain adverse events can be severe and potentially life threatening, but most can be prevented or reversed with close monitoring and appropriate management.

Implications

This family of immune-checkpoint inhibitors benefits not only patients with metastatic melanoma but also those with historically less responsive tumor types. Although a subset of patients responds to single-agent blockade, the initial trial of checkpoint-inhibitor combinations has reported a potential to improve response rates. Combination therapies appear to be a means of increasing response rates, albeit with increased immune-related adverse events. As these treatments become available to patients, education regarding the recognition and management of immune-related effects of immune-checkpoint blockade will be essential for maximizing clinical benefit.


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Krishan Maggon 's curator insight, May 15, 4:02 AM

doi:10.1016/j.clinthera.2015.02.018

 

Clinical Therapeutics

Volume 37, Issue 4, 1 April 2015, Pages 764–782

Review Article The Next Immune-Checkpoint Inhibitors: PD-1/PD-L1 Blockade in MelanomaKathleen M. Mahoney, MD, PhD1, 2, , , Gordon J. Freeman, PhD2, David F. McDermott, MD1

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Scientist Solutions - Monoclonal Antibody Epitope Mapping

Large Searchable List of Antibody protocols online
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Finding should enhance treatments that stop immune system attacks

Finding should enhance treatments that stop immune system attacks | Immunology and Biotherapies | Scoop.it
An important discovery has been made about an immune cell that is already being used in immunotherapy to treat diseases such as type I diabetes. The work details how regulatory T cells can cure inflammatory diseases, researchers say.
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Advances in monoclonal antibody therapy for multiple myeloma

Advances in monoclonal antibody therapy for multiple myeloma | Immunology and Biotherapies | Scoop.it
At the Myeloma 2015 meeting, Dr Joseph Mikhael (Mayo Clinic, Scottsdale, AZ) discusses the development of monoclonal antibodies (mAbs), including anti-CD38 mAbs, SAR650984 and daratumumab, and anti-SLAMF7 mAb, elotuzumab, for the treatment of...
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