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Immunotherapeutic strategies, notably immune checkpoint inhibitors, have become a standard of care for the treatment of advanced cancers, with a growing spectrum of activity. These monoclonal antibodies target the co-inhibitory signals between tumor cells or antigen-presenting cells and T cells, thereby enhancing antitumour T cell activity. However, the occurrence of immune-related adverse events, that can affect all organ-system, represents a major limiting factor to the clinical development of these antibodies. Management of such toxicity requires a close collaboration between oncologists and organ-specialists, by using glucocorticoids and/or other immunosuppressive therapies, with the common objective not alter anti-tumor response., (© 2019 médecine/sciences – Inserm.)

Lung cancer is the leading cause of cancer related deaths worldwide. Since the advent of immunotherapy, survival has significantly improved. Though encouraging treatment results, initially only some patients used to benefit significantly and specifically from immunotherapy administered alone. Recently, different combinations of immunotherapy treatments with cytotoxic chemotherapy and anti-angiogenic treatments were tested in order to improve the results. Six immunotherapy treatment strategies are currently approved in Switzerland for the treatment of advanced lung cancer, either in first or later line of treatment, alone or in combination with other cytotoxic treatments. In this paper we will review the results of the latest clinical trials testing immunotherapy that led to change of the standard of care for non-small cell lung cancer, and will mention the latest perspectives of the treatment for locally advanced cancers and for small cell lung cancer., Competing Interests: Heyfa Meganem, Roxana-Maria Socianu et Ana Dolcan n’ont déclaré aucun conflit d’intérêts en relation avec cet article. Hasna Bouchaab: participation à des comités consultatifs de MSD, BMS, F. Hoffmann-La Roche, AstraZeneca, Novartis, Pfizer et Takeda. Nuria Mederos: participation à des comités consultatifs d’AstraZeneca. Tu Nguyen: a reçu une bourse de formation, a reçu des indemnités en tant que consultant, a donné des conférences et a participé à des comités consultatifs pour AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, F. Hoffmann-La Roche, Merck, Sharp and Dohme, et Novartis, qui lui ont versé des honoraires. Solange Peters a reçu des fonds éducationnels, travaillé comme consultant indépendant et/ou donné des conférences pour: Abbvie, Amgen, AstraZeneca, Bayer, Biocartis, Boehringer-Ingelheim, Bristol-Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, Eli Lilly, F. Hoffmann-La Roche, Foundation Medicine, Illumina, Janssen, Merck Sharp et Dohme, Merck Serono, Merrimack, Novartis, Pharma Mar, Pfizer, Regeneron,Sanofi, Seattle Genetics et Takeda, de qui elle a reçu des honoraires.

The management of cancer patients has changed due to the considerably more frequent use of immune checkpoint inhibitors (ICPI). However, the use of ICPI has a risk of side-effects, particularly endocrine toxicity. Since the indications for ICPI are constantly expanding due to their efficacy, it is important that endocrinologists and oncologists know how to look for this type of toxicity and how to treat it when it arises. In view of this, the French Endocrine Society initiated the formulation of a guidance document on ICPI-related endocrine toxicity. In this paper, we summarize the main insights of experts' opinions, from an oncologist viewpoint: initial screening, monitoring, emergency situations for which immediate management by the oncologist is crucial, as well as the roles of the interactions between oncologists and endocrinologists. These points will be detailed for each endocrinopathy, i.e., dysthyroidism, hypophysitis, fulminant diabetes and primary adrenal insufficiency. In each chapter, expert opinion will be given on the diagnosis, management and monitoring for each complication. Finally, the CTCAE (Common terminology criteria for adverse events) recommendations will be discussed in view of the relatively easy management of such endocrine side-effects., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)

Immunotherapy and Allogeneic Stem Cells Transplantation: Allogeneic stem cell transplantations represent perfect example of immunotherapy. Its positive aspects are due to the graft versus tumor effect. Unfortunately, this therapeutic advantage is usually associated with graft versus host effects. While the mechanism of these two graft reactions remain unclear, this is possible to modulate these immunologic effects. The type of conditioning regimen, the source of donor and the use of donor cells after the transplantation may influence the toxicity and the tumor response, leading to a better optimization of the procedure. This paper is presenting all the parameters which may contribute to improve allogeneic stem cell transplantations., (© 2016 Société Française du Cancer. Publié par Elsevier Masson SAS. Tous droits réservés.)

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Copyright of Oncologie (Tech Science Press) is the property of Tech Science Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The approval of substantial numbers of targeted biologic therapies (e.g., monoclonal antibodies, fusion proteins) for treatment of inflammatory diseases has positioned these drugs as important to fight chronic disorders such as psoriasis, rheumatoid arthritis and Crohn's disease. One of the concerns raised with the administration of biologic therapies is that because most of them are immunogenic glycoproteins they induce undesirable immune response leading to the generation of specific anti-drug antibodies (ADA). The development of "self" derived protein therapeutics (comprised of human germline sequence), such as recombinant "human" antibodies, helped to reduce the production of ADA but did not avoid all immunogenicity. Reduced efficacy and safety issues such as anaphylaxis or vasculitis accompany the development of ADA. In addition to immune reactions directed against the biologic therapies as a whole, some of them such as anti-TNFα are able to induce auto-immune response, notably antinuclear antibody (ANA). ANA development was associated with induced lupus and in psoriasis it was suggested that it may act as a marker of treatment failure to anti-TNFα. With a focus on psoriasis, this paper makes a current point on the consequences and challenges of the development of anti-drug antibodies and auto-immunity in patients who receive biologic therapies., (Copyright © 2012 Elsevier Masson SAS. All rights reserved.)

Objective: Authors reported the results of a study on the application of immunonutrion in peri-operative (pre and postoperative) in head and neck cancer for all patients malnourished or not. In preoperative we used an oral treatmentand in postoperative an enteral one., Materials and Methods: Prospective study concerning 78 patients (47 malnourished versus 31 not) having had heavy head and neck curative cancerology surgery. The mean follow up was of 10 months (from 7 to 16 month). They peri-operative immuno-enriched diet consisted, in pre-operative of 1000 kcal/j during 7 days of oral immunonutrition (Impact), and in post-operative, 1500 kcal/j during 10 days of enteral immunonutition (Crucial). The nutritional state was evaluated in pre-operative by simple clinical and biological parameters (size, weight, CMI "Corporal Mass Index", albumin, NRI "Nutritional Risk Index"), and in post-operative by the evolution of the weight and the CMI. The palatability of the product used in pre-operative and the patients' compliance to the treatment are studied using the satisfaction's multiple choice question paper., Results: The study showed an improvement of the patients' nutritional and general state (regain appetite, less marked asthenia) and of the quality of life. The product used in preoperative was well tolerated, this oral supplementation led to the same beneficial effects of the enteral's. At eight days in preoperative, the average weight was 62.35 kg, the average CMI was 20.93, and the average NRI was 94.12. In post-operative the patients' nutritional state improved: at eight days, the average loss of weight was 2.82 kg, the average CMI was 22.2. At one and six months after respectively the average gain of weight was 2.17 kg and 6.11 kg, the average CMI was 23.71 and 25.16. The application of this protocol decreased the post-operative complications (13% reduction of the infectious complications and 6% diminution of the fistulas). The time of hospitalization is then reduced (1.7 days), and the life's longevity is improved., Conclusion: The results produced by this study, demonstrate the necessity to apply a peri-operative immuno-enriched diet systematically for all the patients with and without a degraded nutritional state, undergoing a heavy head and neck curative cancerology surgery.

The central nervous system is separated from the rest of the body by the blood-brain barrier. This barrier prevents many substances, such as the antibodies, to penetrate into the brain making it difficult to use them for the treatment of brain diseases, such as tetanus and botulism. These two diseases are caused by the development of bacilli of the genus Clostridium which release neurotropic toxins. Specific antibodies can neutralize toxin activity when the toxin is in the blood but are ineffective when it is transported into nerve cells. Various invasive strategies have been used to deliver antibodies to the brain. However, they can induce seizures and transient neurologic deficits and may be applicable only for diseases restricted to the brain surface. Physiologically based strategies utilizing transport systems naturally present at the blood-brain barrier appear to be a more promising approach to brain delivery of antibodies. Cationization is a chemical treatment that causes the conversion of superficial carboxyl groups on a protein into extended primary amino groups. This is used to increase interactions of this protein with the negative charges at the luminal plasma membrane of the brain endothelial cells. The cationized protein can then undergo adsorptive mediated transcytosis through the blood-brain barrier. There are many problems yet to be solved in successfully carrying out in vivo applications of cationized antibodies. One of these problems is that cationization can cause damage to an antibody molecule and, thus, can compromise its binding affinity. Depending on the radiolabelling of the cationized antibodies, a serum inhibition phenomenon can possibly alter the pharmacokinetics and the organ distribution of these molecules. The antibodies can be cationized using various, synthetic (hexamethylenediamine) or naturally occuring (e.g., putrescine) polyamines. Hexamethylenediamine-induced and putrescine-induced brain uptakes of various antibodies and proteins have been shown, but the results obtained suggest that cationization with putrescine may be a more efficient approach to blood-brain barrier delivery. The development of animal or cellular models to check for therapeutic efficacy of cationized antibodies is necessary. In spite of the difficulties, the studies described in this paper indicate that cationization can be a realistic delivery strategy for carrying antibodies across the blood-brain barrier. The advances made in antibody technologies help generate more appropriate immunological structures for brain transfer with better effector functions and decreased immunogenicity or toxicity. Taken together, these two aspects can lead to further developments in treatment of intoxications caused by the clostridial neurotoxins.

Objective: To examine three typical disease states seen in intensive care, sepsis, Fulminant purpura and acute respiratory distress syndrome (ARDS) to assess the implication of cytokines in their pathogenesis and particularly in the clinical applications of possible cytokine inhibitors., Source of Data: The data bank of MedLine and the Index Medicus 1985-1993 and the first part of 1994. These sources have enabled us to consult publications in French and English and to include information on both animals and humans. The publications issued from Intensive Care Congresses have also been scrutinised; the Société de Réanimation de Langue Française, The American Thoracic Society and the 13th and 14th International Symposium on Intensive Care and Emergency Medicine, Brussels. SELECTION OF DATA: This review emphasizes certain areas of work including recognised work which has been published on the immunotherapy of sepsis in man, on those papers which have been published as a preliminary communication in the from of a summary and on certain papers relating to animal work which are regularly cited in Intensive Care literature., Discussion: The relationship between cytokines and the three selected disease states have been briefly described. The greater part of those papers which have either been published or are in the process of being published present pharmacotherapeutic data in phase 2 or phase 3 in relationship to anticytokines and sepsis. As for the treatment of Fulminant purpura and ARDS, using anticytokine antibodies in 1994 we are still in the stage of hypothesis and speculation., Conclusions: Future clinical strategies designed to combat. Future clinical strategies designed to fight against the most critical diseases in intensive care medicine require some use of any kind of immunotherapy. In animal studies, convincing data are available showing that immunotherapy improves the prognosis of sepsis, whereas in humans, to date, the results appear to be deceiving. Future research in this direction is mandatory, in sepsis and in other disease states, like ARDS, because no other hope for treating these patients seems to appear in a near future.

Copyright of Annales Françaises de Médecine d'Urgence is the property of John Libbey Eurotext Ltd. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

I.--Treatment with BCG and DDS in lepromatous or borderline patients. II.--Value of BCG added to a prior and long-continued treatment with DDS or rifamipicine. III.--Value of various immunostimulants given previously to a treatment with BCG and chemotherapy. IV.--Value of lysate of Neisseria perflava as an immunostimulant associated with DDS in an initial treatment of lepromatous and borderline patients. V.--Results of a seventeen months treatment of lepromatous and borderline patients with a lysate of Neisseria perflava associated with DDS. The various therapeutic trials reported in these 5 papers demonstrate that hansenian nevritis conventionnally treated may show improvement when an immunostimulant (BCG or bacterial lysate or levamisole) is given either previously or in association with DDS or rifampicine or after such a treatment. It has still been observed that two immunostimulants given simultaneously have no good effect and that this association must be discarded.

Copyright of Oncologie (Tech Science Press) is the property of Tech Science Press and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)