scholarly journals Considering B7-CD28 as a family through sequence and structure

2019 ◽  
Vol 244 (17) ◽  
pp. 1577-1583
Author(s):  
Sean M West ◽  
Xiaodi A Deng
Keyword(s):  
Immune Response ◽  
Cytotoxic T Lymphocyte ◽  
Treatment Options ◽  
Cell Receptor ◽  
Therapeutic Agents ◽  
Cancer Treatments ◽  
Durable Response ◽  
Term Survival ◽  
History Of ◽  
Immunoglobulin Fold

With the emergence of immuno-oncology, new therapeutic agents that modulate immune activation and regulation are being used to treat cancer patients with durable response. It is well known that following T-cell receptor (TCR) activation, many co-receptors can augment or suppress the TCR signal, and therapeutically targeting these co-receptors has proven effective. The B7-CD28 family is comprised of such immune-regulatory receptors, and antibodies against its members programmed cell death protein 1 (PD-1), programmed death-ligand 1 (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) have revolutionized cancer treatment. These therapies promote an immune response against tumor cells, which demonstrated better long-term survival and tolerability compared to traditional cancer treatments. In this review we describe the history of the expanding B7-CD28 family, and by comparison of sequence and structure reveal that it is a non-traditional family. The family has grown to include proteins that share low sequence identity, generally grouped by regulation of immune response, which utilize the common immunoglobulin fold. This low level of commonality has provided additional challenges to the drug discovery process as the mechanisms and therapeutic potency between family members can vary greatly. Impact statement Immunotherapy as a field has dramatically expanded in the last decade in the area of oncology with efficacy demonstrated by PD-1, PD-L1, and CTLA-4 blockade. With all three “checkpoint blockade” receptors being in the B7-CD28 family, there has been increased interest in targeting other members in this family due to redundancy in immune regulation, i.e., the combination of therapeutic agents targeting multiple co-inhibitory receptors may yield additional antitumor efficacy. Therefore significant resources are being dedicated to developing additional B7-CD28 treatment options.

Immunotherapy for advanced melanoma: current situation in Japan

2020 ◽  
Vol 51 (1) ◽  
pp. 3-9
Author(s):  
Junji Kato ◽  
Hisashi Uhara
Keyword(s):  
Uveal Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Advanced Melanoma ◽  
Current Evidence ◽  
Clinical Effects ◽  
Durable Response ◽  
Term Survival

Abstract Treatment with immune checkpoint inhibitors provides long-term survival for patients with advanced melanoma. Improvements in the overall survival of advanced melanoma patients have been achieved with anti-PD-1 monotherapy and anti-PD-1+ CTLA4 combination therapy, but there are still many issues to resolve. Acral, mucosal and uveal melanoma have been less responsive to immune checkpoint inhibitors than cutaneous melanoma. For patients who have achieved a good response, it is still not known how long the anti-PD-1 therapy should be administered. Moreover, there is limited treatment for patients who relapse during or after adjuvant anti-PD-1 therapy. Here, we review the current evidence regarding the clinical effects of immunotherapy for advanced melanoma. Moreover, we review previous studies of acral, mucosal and uveal melanoma, and we discuss the recent findings regarding durable response after the cessation of anti-PD-1 therapy, and treatment options for recurrence after adjuvant therapy.

scholarly journals Oligoclonal expansion of major histocompatibility complex class I-restricted cytolytic T lymphocytes during a primary immune response in vivo: direct monitoring by flow cytometry and polymerase chain reaction.

1993 ◽  
Vol 177 (5) ◽  
pp. 1487-1492 ◽  
Author(s):  
H R MacDonald ◽  
J L Casanova ◽  
J L Maryanski ◽  
J C Cerottini
Keyword(s):  
Flow Cytometry ◽  
Immune Response ◽  
Polymerase Chain Reaction ◽  
Cytotoxic T Lymphocyte ◽  
Cell Receptor ◽  
Primary Response ◽  
Primary Immune Response ◽  
Chain Reaction ◽  
Polymerase Chain

Previous T cell receptor (TCR) sequence analysis of a panel of 23 H-2Kd restricted cytotoxic T lymphocyte (CTL) clones recognizing the decapeptide HLA-CW3 170-179 revealed a striking conservation of TCR structure, in that all clones examined used V beta 10 and J alpha pHDS58 segments. We show here that the primary response in vivo after intraperitoneal injection of DBA/2 mice with HLA-CW3 expressing transfectants of syngeneic P815 (H-2d) tumor cells is characterized by a dramatic expansion of CD8+ V beta 10+ CTL in the peritoneal cavity and draining (mesenteric) lymph node, as well as in peripheral blood. Additional analysis of TCR on HLA-CW3 immune populations by flow cytometry and polymerase chain reaction further indicates that the vast majority of responding CD8+ cells express restricted V alpha domains, a dominant J alpha segment (pHDS58), and a conserved CDR3 length for both alpha and beta chains. This novel system provides a unique opportunity to directly monitor an oligoclonal primary antigen specific immune response in vivo at the single cell level independently of functional assays.

scholarly journals Anti-CD2 antibodies induce T cell unresponsiveness in vivo.

1991 ◽  
Vol 174 (5) ◽  
pp. 957-967 ◽  
Author(s):  
B Gückel ◽  
C Berek ◽  
M Lutz ◽  
P Altevogt ◽  
V Schirrmacher ◽  
...  
Keyword(s):  
Immune Response ◽  
T Cells ◽  
T Cell ◽  
Cytotoxic T Lymphocyte ◽  
Tumor Cell Line ◽  
Cell Receptor ◽  
T Cell Response ◽  
Signal Molecule

The CD2 receptor functions as an adhesion and signal molecule in T cell recognition. Multimeric binding of CD2 on T cells to its physiologic ligand LFA-3 on cognate partner cells in vitro efficiently augments the antigen-specific T cell signal delivered by the T cell receptor/CD3 complex. The precise contribution of the antigen-nonspecific CD2-LFA-3 interactions to T cell immune responses in vivo, however, has been difficult to assess. Here we analyzed the role of CD2 in the murine immune response using a nondepleting anti-CD2 monoclonal antibody that induces a marked, reversible modulation of CD2 expression on murine T and B cells in situ. This modulation is dose and time dependent, specific for CD2, and does not require the Fc portion of the antibody. Anti-CD2 antibodies [rat IgG1 or F(ab')2] significantly inhibit the CD4+ T cell-mediated response to hen egg lysozyme and the cytotoxic CD8+ T cell response to a syngeneic tumor cell line. In both cases, anti-CD2 antibodies are only effective when administered before or within 24 h after antigen priming. The suppression of the antitumor response corresponds to a sixfold reduction of specific cytotoxic T lymphocyte precursor cells and results in the abrogation of protective antitumor immunity. Anti-CD2 antibodies also affect the humoral immune response to oxazolone: the isotype switch from specific IgM to IgG1 antibodies is delayed, whereas the IgM response is unaltered. In addition, a single antibody injection results in sustained polyclonal unresponsiveness of T cells irrespective of antigen priming and CD2 modulation. These results document that CD2-mediated signals induce a state of T cell unresponsiveness in vivo.

scholarly journals Systemic Therapy for Hepatocellular Carcinoma: Latest Advances

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 412 ◽  
Author(s):  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Trials ◽  
Combination Therapy ◽  
Systemic Therapy ◽  
Cytotoxic T Lymphocyte ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Phase Iii ◽  
Term Survival ◽  
Targeted Agent

Systemic therapy for hepatocellular carcinoma (HCC) has changed drastically since the introduction of the molecular targeted agent sorafenib in 2007. Although sorafenib expanded the treatment options for extrahepatic spread (EHS) and vascular invasion, making long-term survival of patients with advanced disease achievable to a certain extent, new molecular-targeted agents are being developed as alternatives to sorafenib due to shortcomings such as its low response rate and high toxicity. Every single one of the many drugs developed during the 10-year period from 2007 to 2016 was a failure. However, during the two-year period from 2017 through 2018, four drugs—regorafenib, lenvatinib, cabozantinib, and ramucirumab—emerged successfully from clinical trials in quick succession and became available for clinical use. The efficacy of combination therapy with transcatheter arterial chemoembolization (TACE) plus sorafenib was also first demonstrated in 2018. Recently, immune checkpoint inhibitors have been applied to HCC treatment and many phase III clinical trials are ongoing, not only on monotherapy with nivolumab, pembrolizumab, and tislelizumab, but also on combination therapy with checkpoint inhibitors, programmed death-1 (PD-1) or PD-ligand 1 (PD-L1) antibody plus a molecular targeted agent (bevacizumab) or the cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibody, tremelimumab. These combination therapies have shown higher response rates than PD-1/PD-L1 monotherapy alone, suggesting a synergistic effect by combination therapy in early phases; therefore, further results are eagerly awaited.

Új lehetőségek a refrakter és relabált Hodgkin-lymphomás betegek kezelésében

2015 ◽  
Vol 156 (45) ◽  
pp. 1824-1833 ◽  
Author(s):  
Árpád Illés ◽  
Ádám Jóna ◽  
Zsófia Simon ◽  
Miklós Udvardy ◽  
Zsófia Miltényi
Keyword(s):  
Stem Cell ◽  
Hodgkin Lymphoma ◽  
Treatment Options ◽  
Survival Rates ◽  
Relapse Free Survival ◽  
Term Survival ◽  
Free Survival ◽  
Novel Treatment ◽  
Refractory Hodgkin Lymphoma

Introduction: Hodgkin lymphoma is a curable lymphoma with an 80–90% long-term survival, however, 30% of the patients develop relapse. Only half of relapsed patients can be cured with autologous stem cell transplantation. Aim: The aim of the authors was to analyze survival rates and incidence of relapses among Hodgkin lymphoma patients who were treated between January 1, 1980 and December 31, 2014. Novel therapeutic options are also summarized. Method: Retrospective analysis of data was performed. Results: A total of 715 patients were treated (382 men and 333 women; median age at the time of diagnosis was 38 years). During the studied period the frequency of relapsed patients was reduced from 24.87% to 8.04%. The numbers of autologous stem cell transplantations was increased among refracter/relapsed patients, and 75% of the patients underwent transplantation since 2000. The 5-year overall survival improved significantly (between 1980 and 1989 64.4%, between 1990 and 1999 82.4%, between 2000 and 2009 88.4%, and between 2010 and 2014 87.1%). Relapse-free survival did not change significantly. Conclusions: During the study period treatment outcomes improved. For relapsed/refractory Hodgkin lymphoma patients novel treatment options may offer better chance for cure. Orv. Hetil., 2015, 156(45), 1824–1833.

Long-term survival of the nasal NK/T cell lymphoma

2008 ◽  
Vol 149 (17) ◽  
pp. 801-805
Author(s):  
Péter Rajnics ◽  
László Krenács ◽  
András Kenéz ◽  
Zoltán Járay ◽  
Enikő Bagdi ◽  
...  
Keyword(s):  
T Cell ◽  
Treatment Guidelines ◽  
Cell Lymphoma ◽  
Treatment Options ◽  
Diagnostic Procedures ◽  
T Cell Lymphoma ◽  
Term Survival ◽  
Barr Virus ◽  
Significant Difference ◽  
Nk T Cell

The nasal NK/T cell lymphoma is a rare, extranodal non-Hodgkin lymphoma in western civilizations, which has poor prognosis. The Epstein–Barr virus can be detected in tumor cells in nearly all cases. There are no definite treatment guidelines in our days. There is no significant difference in survival between radiotherapy and chemotherapy according to Asian studies. In this case study we show our diagnostic procedures, our treatment options and we present the summary of this illness based on the data found in the literature.

Immunotherapy in cancer: mechanisms of immune response and their place in cancer treatments

2017 ◽  
Vol 1 (38) ◽  
Author(s):  
Dana Lucia Stănculeanu ◽  
Carmen Ardeleanu ◽  
Daniela Zob ◽  
Raluca Ioana Mihăilă ◽  
Oana Cătălina Toma ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Treatments

Safety of a Clozapine Trial Following Quetiapine-Induced Leukopenia: A Case Report

2019 ◽  
Vol 14 (1) ◽  
pp. 80-83 ◽  
Author(s):  
Asma H. Almaghrebi
Keyword(s):  
Treatment Options ◽  
Young Female ◽  
Similar Reaction ◽  
Careful Monitoring ◽  
Treatment Resistant ◽  
Blood Cell Count ◽  
Antipsychotic Medications ◽  
Case Presentation ◽  
Clozapine Treatment ◽  
History Of

Background: The clozapine-derivative quetiapine has been shown in some cases to cause leukopenia and neutropenia. Case Presentation: We reported on a case of a young female diagnosed with treatment-resistant schizophrenia. After failed trials of three antipsychotic medications and despite a history of quetiapineinduced leukopenia, clozapine treatment was introduced due to the severity of the patient’s symptoms, the limited effective treatment options, and a lack of guidelines on this issue. Result: Over a ten-week period of clozapine treatment at 700 mg per day, the patient developed agranulocytosis. Her white blood cell count sharply dropped to 1.6 &#215; 10<sup>9</sup> L, and her neutrophils decreased to 0.1 &#215; 10<sup>9</sup> L. There had been no similar reaction to her previous medications (carbamazepine, risperidone, and haloperidol). Conclusion: The safety of clozapine in a patient who has previously experienced leukopenia and neutropenia with quetiapine requires further investigation. Increased attention should be paid to such cases. Careful monitoring and slow titration are advisable.

Primary squamous cell carcinoma of the ampulla of Vater: management and review of the literature

2021 ◽  
Vol 14 (1) ◽  
pp. e236477
Author(s):  
Subhash Soni ◽  
Poonam Elhence ◽  
Vaibhav Kumar Varshney ◽  
Sunita Suman
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Survival Rates ◽  
Ampulla Of Vater ◽  
Metallic Stent ◽  
Biological Behaviour ◽  
Curative Intent ◽  
Term Survival ◽  
History Of

Squamous cell carcinoma (SCC) of the ampulla of Vater is a rare pathology and only few cases are reported in the literature. With limited experience of primary SCC in the ampulla of Vater, its biological behaviour, prognosis and long-term survival rates are not well known. A 38-year-old woman presented with a history of painless progressive jaundice for which self-expending metallic stent was placed 3 years back. She was evaluated and initially diagnosed as probably periampullary adenocarcinoma. She underwent pancreaticoduodenectomy and histopathology with immunohistochemistry was suggestive of SCC of ampulla of Vater. She received adjuvant chemotherapy and doing well with no recurrence after 1 year of follow-up. In conclusion, SCC of the ampulla is an unusual pathology that should be kept as a differential diagnosis for periampullary tumours. Surgical treatment with curative intent should be performed whenever feasible even in the setting of bulky tumour to improve the outcome.

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