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Clinical Microbiology and Infection :... Jun 2018The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies. (Review)
Review
ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies: an infectious diseases perspective (Agents targeting lymphoid or myeloid cells surface antigens [II]: CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4).
BACKGROUND
The present review is part of the ESCMID Study Group for Infections in Compromised Hosts (ESGICH) Consensus Document on the safety of targeted and biological therapies.
AIMS
To review, from an Infectious Diseases perspective, the safety profile of agents targeting CD22, CD30, CD33, CD38, CD40, SLAMF-7 and CCR4 and to suggest preventive recommendations.
SOURCES
Computer-based MEDLINE searches with MeSH terms pertaining to each agent or therapeutic family.
CONTENT
The risk and spectrum of infections in patients receiving CD22-targeted agents (i.e. inotuzumab ozogamicin) are similar to those observed with anti-CD20 antibodies. Anti-Pneumocystis prophylaxis and monitoring for cytomegalovirus (CMV) infection is recommended for patients receiving CD30-targeted agents (brentuximab vedotin). Due to the scarcity of data, the risk posed by CD33-targeted agents (gemtuzumab ozogamicin) cannot be assessed. Patients receiving CD38-targeted agents (i.e. daratumumab) face an increased risk of varicella-zoster virus (VZV) infection. Therapy with CD40-targeted agents (lucatumumab or dacetuzumab) is associated with opportunistic infections similar to those observed in hyper-IgM syndrome, and prevention strategies (including anti-Pneumocystis prophylaxis and pre-emptive therapy for CMV infection) are warranted. SLAMF-7 (CD319)-targeted agents (elotuzumab) induce lymphopenia and increase the risk of infection (particularly due to VZV). The impact of CCR4-targeted agents (mogamulizumab) on infection susceptibility is difficult to distinguish from the effect of underlying diseases and concomitant therapies. However, anti-Pneumocystis and anti-herpesvirus prophylaxis and screening for chronic hepatitis B virus (HBV) infection are recommended.
IMPLICATIONS
Specific management strategies should be put in place to reduce the risk and/or the severity of infectious complications associated to the reviewed agents.
Topics: ADP-ribosyl Cyclase 1; Antigens, Surface; Biological Therapy; CD40 Antigens; Clinical Trials as Topic; Communicable Diseases; Consensus; Humans; Immunocompromised Host; Ki-1 Antigen; Lymphocytes; Membrane Glycoproteins; Molecular Targeted Therapy; Myeloid Cells; Receptors, CCR4; Sialic Acid Binding Ig-like Lectin 2; Sialic Acid Binding Ig-like Lectin 3; Signaling Lymphocytic Activation Molecule Family
PubMed: 29572070
DOI: 10.1016/j.cmi.2018.03.022 -
Methods and Findings in Experimental... Dec 2009[Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate,...
[Methoxy-(11)C]PD-153035, 2-Methoxyestradiol; Adalimumab, Adecatumumab, Adefovir dipivoxil, ADH-1, ADX-10059, Aflibercept, AIR-human growth hormone, Aliskiren fumarate, AMG-221, Amlodipine besylate/olmesartan medoxomil, Aprepitant; Bavituximab, Bevacizumab, Bexarotene, BIBW-2992, BMS-690514, Bortezomib, Bosentan, Briakinumab; Capecitabine, Certolizumab pegol, Cetuximab, Cholecalciferol, Choline fenofibrate, Chorionic gonadotropin (human), Cixutumumab, Clopidogrel, CP-690550 citrate; Dabigatran, Dacetuzumab, Daclizumab, Dapagliflozin, Darbepoetin alfa, Dasatinib, Denosumab; Efavirenz, Elisidepsin, Enoxaparin, Enzastaurin hydrochloride, Eribulin mesilate, Erlotinib hydrochloride, Everolimus, Exenatide; Fenobam, Figitumumab, Filibuvir, Fondaparinux sodium, Fresolimumab; Gefitinib, Golimumab, Golnerminogene pradenovec; Ifosfamide, Imatinib mesylate, Ipilimumab, Ivabradine hydrochloride, Ixabepilone; Lapatinib ditosylate, Lenalidomide, Levocetirizine dihydrochloride, Liposomal vincristine, Liraglutide; M-118, Masitinib mesylate, Metformin hydrochloride, Micafungin sodium, Moxifloxacin hydrochloride; Neratinib; Oblimersen sodium, Ofatumumab, Olmesartan medoxomil; Paclitaxel nanoparticles, Palifosfamide lysine, Panobacumab, Panobinostat, Patupilone, Peginterferon alfa-2a, Pegylated arginine deiminase 20000, Piclozotan hydrochloride hydrate, Pixantrone maleate, Prasterone, Prasugrel, Prednisone, Progesterone, Prucalopride, pVGI.1 (VEGF-2); Retigabine, rhFSH, Rituximab, Rivaroxaban, Rosuvastatin calcium; Salinosporamide A, Selumetinib, Sipuleucel-T, Somatropin, Sorafenib, SSR-244738, Sunitinib malate; Tamoxifen citrate, Teduglutide, Telavancin hydrochloride, Telmisartan, Telmisartan/amlodipine, Telmisartan/hydrochlorothiazide, Temsirolimus, Tenofovir disoproxil fumarate, Tipifarnib, Tolvaptan, Trastuzumab, Trastuzumab-MCC-DM1, Travoprost, Tremelimumab; Valsartan/amlodipine besylate, Valsartan/amlodipine besylate/hydrochlorothiazide, Valsartan/hydrochlorothiazide, Vandetanib, Vorinostat.
Topics: Clinical Trials as Topic; Humans
PubMed: 20140276
DOI: No ID Found -
Current Hematologic Malignancy Reports Oct 2008The treatment of non-Hodgkin lymphoma (NHL) has changed dramatically since the introduction of rituximab, a monoclonal antibody that binds to the B-cell transmembrane... (Review)
Review
The treatment of non-Hodgkin lymphoma (NHL) has changed dramatically since the introduction of rituximab, a monoclonal antibody that binds to the B-cell transmembrane protein CD20 and causes lysis of the lymphoma cells. Since then, a number of additional antibodies have been tested against other B-cell targets, resulting in variable efficacies. The goal of these newer agents is to achieve similar or better response rates as seen with rituximab and perhaps demonstrate activity in rituximab-refractory disease. Several of the antibodies have been investigated in combination with each other as well as with conventional chemotherapeutic regimens. Approval of such antibodies by regulatory committees and their eventual integration into clinical practice will likely depend on positive results from randomized trials.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal, Murine-Derived; Antibodies, Neoplasm; Antineoplastic Agents; Clinical Trials as Topic; Humans; Lymphoma, B-Cell; Rituximab
PubMed: 20425465
DOI: 10.1007/s11899-008-0027-5 -
BMC Cancer Oct 2010Developing the right drugs for the right patients has become a mantra of drug development. In practice, it is very difficult to identify subsets of patients who will...
BACKGROUND
Developing the right drugs for the right patients has become a mantra of drug development. In practice, it is very difficult to identify subsets of patients who will respond to a drug under evaluation. Most of the time, no single diagnostic will be available, and more complex decision rules will be required to define a sensitive population, using, for instance, mRNA expression, protein expression or DNA copy number. Moreover, diagnostic development will often begin with in-vitro cell-line data and a high-dimensional exploratory platform, only later to be transferred to a diagnostic assay for use with patient samples. In this manuscript, we present a novel approach to developing robust genomic predictors that are not only capable of generalizing from in-vitro to patient, but are also amenable to clinically validated assays such as qRT-PCR.
METHODS
Using our approach, we constructed a predictor of sensitivity to dacetuzumab, an investigational drug for CD40-expressing malignancies such as lymphoma using genomic measurements of cell lines treated with dacetuzumab. Additionally, we evaluated several state-of-the-art prediction methods by independently pairing the feature selection and classification components of the predictor. In this way, we constructed several predictors that we validated on an independent DLBCL patient dataset. Similar analyses were performed on genomic measurements of breast cancer cell lines and patients to construct a predictor of estrogen receptor (ER) status.
RESULTS
The best dacetuzumab sensitivity predictors involved ten or fewer genes and accurately classified lymphoma patients by their survival and known prognostic subtypes. The best ER status classifiers involved one or two genes and led to accurate ER status predictions more than 85% of the time. The novel method we proposed performed as well or better than other methods evaluated.
CONCLUSIONS
We demonstrated the feasibility of combining feature selection techniques with classification methods to develop assays using cell line genomic measurements that performed well in patient data. In both case studies, we constructed parsimonious models that generalized well from cell lines to patients.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Cell Line; Cell Line, Tumor; Data Interpretation, Statistical; Drug Screening Assays, Antitumor; Genomics; Humans; Lymphoma; Models, Statistical; Oligonucleotide Array Sequence Analysis; Prognosis; RNA, Messenger; Regression Analysis; Reverse Transcriptase Polymerase Chain Reaction; Treatment Outcome
PubMed: 20979617
DOI: 10.1186/1471-2407-10-586 -
Methods and Findings in Experimental... 2009(-)-Gossypol; Alemtuzumab, Amlodipine, Anakinra, Azacitidine; Bazedoxifene acetate, Belinostat, Bevacizumab, BI-201335, BI-2536, Biphasic insulin aspart, Bortezomib;...
(-)-Gossypol; Alemtuzumab, Amlodipine, Anakinra, Azacitidine; Bazedoxifene acetate, Belinostat, Bevacizumab, BI-201335, BI-2536, Biphasic insulin aspart, Bortezomib; Cetuximab, CNTO-328, Custirsen sodium; Dacetuzumab; Elacytarabine, Erlotinib hydrochloride, Everolimus, Exenatide; Forodesine hydrochloride, Fostamatinib disodium, Frovatriptan; Ibutamoren mesilate, Imatinib mesylate, IMC-18F1, INCB-18424, Indacaterol, Insulin detemir, Insulin glargine, Insulin glulisine; KW-0761, KW-2449; Lapatinib ditosylate, Liraglutide; MK-2461, Mycophenolic acid sodium salt; Peginterferon alfa-2a, Pemetrexed disodium, Pioglitazone hydrochloride/metformin hydrochloride, Pregabalin; rBCG-30; Satraplatin, SB-743921, Short ragweed pollen allergenic extract, SNS-314, Sorafenib, Sugammadex sodium, Sunitinib malate; Teriparatide; Valsartan/amlodipine besylate, Vinflunine, Vorinostat.
Topics: Clinical Trials as Topic; Humans
PubMed: 19357798
DOI: No ID Found -
Science Translational Medicine Mar 2011The primary function of B cells, critical components of the adaptive immune response, is to produce antibodies against foreign antigens, as well as to perform isotype...
The primary function of B cells, critical components of the adaptive immune response, is to produce antibodies against foreign antigens, as well as to perform isotype class switching, which changes the heavy chain of an antibody so that it can interact with different repertoires of effector cells. CD40 is a member of the tumor necrosis factor superfamily of cell surface receptors that transmits survival signals to B cells. In contrast, in B cell cancers, stimulation of CD40 signaling results in a heterogeneous response in which cells can sometimes undergo cell death in response to treatment, depending on the system studied. We found an association between sensitivity to CD40 stimulation and mutation of the tumor suppressor p53 in a panel of non-Hodgkin's lymphoma cell lines. Consistent with p53's tumor suppressor role, we found that higher levels of intrinsic DNA damage and increased proliferation rates, as well as higher levels of BCL6, a transcriptional repressor proto-oncogene, were associated with sensitivity to CD40 stimulation. In addition, CD40 treatment-resistant cell lines were sensitized to CD40 stimulation after the introduction of DNA-damaging agents. Using gene expression analysis, we also showed that resistant cell lines exhibited a preexisting activated CD40 pathway and that an mRNA expression signature comprising CD40 target genes predicted sensitivity and resistance to CD40-activating agents in cell lines and mouse xenograft models. Finally, the gene signature predicted tumor shrinkage and progression-free survival in patients with diffuse large B cell lymphoma treated with dacetuzumab, a monoclonal antibody with partial CD40 agonist activity. These data show that CD40 pathway activation status may be useful in predicting the antitumor activity of CD40-stimulating therapeutic drugs.
Topics: Animals; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; B-Lymphocytes; CD40 Antigens; CD40 Ligand; Cell Line, Tumor; Gene Expression Profiling; Humans; Immunotherapy; In Situ Hybridization, Fluorescence; Lymphoma, Large B-Cell, Diffuse; Mice; Microarray Analysis; Proto-Oncogene Mas; Transplantation, Heterologous; Tumor Suppressor Protein p53
PubMed: 21411738
DOI: 10.1126/scitranslmed.3001620 -
Nihon Rinsho. Japanese Journal of... Jan 2015Multiple myeloma (MM) remains mostly incurable despite the recent progress in the treatment strategy. One of novel fields for anti-MM therapeutic strategy is the...
Multiple myeloma (MM) remains mostly incurable despite the recent progress in the treatment strategy. One of novel fields for anti-MM therapeutic strategy is the development of immunotherapy using monoclonal antibodies (MoAbs) against myeloma-specific antigens. This article focuses on the basic and clinical aspects of several emerging and promising novel MoAbs for MM, such as elotuzumab which targets CS1 and daratumumab which targets CD38. Both antigens are highly expressed in more than 90% of MM patients, and the clinical trials have shown promising anti-MM effects, especially in combination with immunomodulatory agent lenalidomide. We also discuss the characteristics and the results of clinical trials of other MoAbs, such as tabalumab against B cell activating factor or dacetuzumab against CD40, being developed for MM.
Topics: ADP-ribosyl Cyclase 1; Antibodies, Monoclonal; B-Cell Activating Factor; Humans; Intercellular Signaling Peptides and Proteins; Multiple Myeloma; Peptides
PubMed: 25626316
DOI: No ID Found