Severity: Warning
Message: file_get_contents(https://...@gmail.com&api_key=61f08fa0b96a73de8c900d749fcb997acc09): Failed to open stream: HTTP request failed! HTTP/1.1 429 Too Many Requests
Filename: helpers/my_audit_helper.php
Line Number: 143
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 143
Function: file_get_contents
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 209
Function: simplexml_load_file_from_url
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3098
Function: getPubMedXML
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Severity: Warning
Message: Attempt to read property "Count" on bool
Filename: helpers/my_audit_helper.php
Line Number: 3100
Backtrace:
File: /var/www/html/application/helpers/my_audit_helper.php
Line: 3100
Function: _error_handler
File: /var/www/html/application/controllers/Detail.php
Line: 574
Function: pubMedSearch_Global
File: /var/www/html/application/controllers/Detail.php
Line: 488
Function: pubMedGetRelatedKeyword
File: /var/www/html/index.php
Line: 316
Function: require_once
Antagonistic monoclonal antibodies (mAbs) targeting inhibitory immune checkpoints have revolutionized the field of oncology. CTLA-4, PD-1, and LAG3 are three co-inhibitory receptors, which can be expressed by subsets of T cells and which play a role in the regulation of adaptive immune responses. Blocking these immune checkpoints receptors (or their ligands) with antagonistic antibodies can lead to tumor regressions and lasting remissions in some patients with cancer. Two anti-CTLA4, six anti-PD1, three anti-PD-L1, and one anti-LAG3 antibodies are currently approved by the FDA and EMA. Their mechanism of action, safety, and efficacy are linked to their affinity with Fc gamma receptors (FcγR) (so called "effector functions"). The anti-CTLA-4 antibodies ipilimumab (IgG1) and tremilimumab (IgG2a), and the anti-PD-L1 avelumab (IgG1) have isotypes with high affinity for activating FcγR and thereby can induce ADCC/ADCP. The effector function is required for the in vivo efficacy of anti-CTLA4 antibodies. For anti-PD(L)1 antibodies, where a pure antagonistic function ("checkpoint blockade") is sufficient, some mAbs are IgG1 but have been mutated in their Fc sequence (e.g., durvalumab and atezolizumab) or are IgG4 (e.g., nivolumab and pembrolizumab) to have low affinity for FcγR. Here, we review the impact of FcγR effector function on immune checkpoint blockers safety and efficacy in oncology.
Download full-text PDF |
Source |
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http://dx.doi.org/10.1111/imr.13427 | DOI Listing |
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11659940 | PMC |
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