Severity: Warning
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Filename: drivers/Session_files_driver.php
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File: /var/www/html/index.php
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Function: require_once
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Filename: Session/Session.php
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File: /var/www/html/index.php
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Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 249
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 249
Function: _error_handler
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Function: require_once
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Message: strpos(): Passing null to parameter #1 ($haystack) of type string is deprecated
Filename: models/Detail_model.php
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File: /var/www/html/application/models/Detail_model.php
Line: 71
Function: strpos
File: /var/www/html/application/controllers/Detail.php
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Function: insertAPISummary
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Function: require_once
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Filename: helpers/my_audit_helper.php
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File: /var/www/html/application/helpers/my_audit_helper.php
Line: 8919
Function: str_replace
File: /var/www/html/application/controllers/Detail.php
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Function: formatAIDetailSummary
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Function: require_once
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Message: Undefined array key "choices"
Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
Line: 316
Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 256
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File: /var/www/html/application/controllers/Detail.php
Line: 256
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
Severity: Warning
Message: Undefined array key "usage"
Filename: controllers/Detail.php
Line Number: 257
Backtrace:
File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Trying to access array offset on value of type null
Filename: controllers/Detail.php
Line Number: 257
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File: /var/www/html/application/controllers/Detail.php
Line: 257
Function: _error_handler
File: /var/www/html/index.php
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Function: require_once
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
Line: 258
Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
File: /var/www/html/index.php
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Message: Undefined array key "usage"
Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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Function: _error_handler
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Filename: controllers/Detail.php
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File: /var/www/html/application/controllers/Detail.php
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Function: _error_handler
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Function: require_once
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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
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File: /var/www/html/application/helpers/my_audit_helper.php
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Function: file_get_contents
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Function: simplexml_load_file_from_url
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Function: getPubMedXML
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Function: GetPubMedArticleOutput_2016
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Function: pubMedSearch_Global
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Purpose: We recently discovered that anti-TIP1 antibody activates endocytosis in cancer cells, which facilitates retention of antibody and dissociation of a conjugated drug. To improve the pharmacokinetics and cancer specificity of radiosensitizing drugs, we utilized antibody-drug conjugates (ADCs) that bind specifically to radiation-inducible antigen, TIP1, on non-small cell lung cancer (NSCLC). This approach exploits the long circulation time of antibodies to deliver a radiosensitizing drug to cancer each day during radiotherapy.
Experimental Design: Antibodies to TIP1 were prioritized based on affinity, cancer-specific binding, and internalization. The lead antibody, 7H5, was conjugated with a cytotoxic drug MMAE because of its ability to radiosensitize cancer. Cytotoxicity, colony formation, and tumor growth studies were performed with 7H5-VcMMAE in combination with radiation.
Results: 7H5 showed a high affinity to recombinant TIP1 protein and radiation-inducible TIP1 on the cancer cell surface. 7H5 undergoes endocytosis in NSCLC cells . We obtained an average drug-to-antibody ratio (DAR) of 4.25 for 7H5-VcMMAE. A 70% reduction in viable cells was observed following 7H5-VcMMAE treatment compared with 7H5 alone in both A549 and H1299 cells. 7H5-VcMMAE sensitized NSCLC cells to radiation, thereby significantly decreasing the surviving fraction. The ADC combined with radiation showed a prolonged delay in tumor growth and improved survival in A549 and H1299 tumor models.
Conclusions: Targeting radiation-inducible TIP1 with a radiosensitizing ADC is a promising strategy to enhance the therapeutic efficacy of NSCLC. This novel approach of targeting with ADCs to radiation-inducible antigens will lead to clinical trials in lung cancer patients treated with radiotherapy.
Download full-text PDF |
Source |
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9167454 | PMC |
http://dx.doi.org/10.1158/1078-0432.CCR-20-1725 | DOI Listing |
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