Pub Date : 2024-12-20DOI: 10.1016/j.iotech.2024.101040
B.E. Nelson , A. Naing , S. Fu , R.A. Sheth , R. Murthy , S. Piha-Paul
Immune checkpoint inhibitors (ICIs) have revolutionized oncology, yielding remarkable and durable responses in various cancers. However, a significant proportion of patients develop resistance to ICIs. The tumor microenvironment plays a critical role in immunotherapy resistance, characterized by immune cell composition, regulatory factors, and tumor mutational burden. Intratumoral immunotherapy, involving direct injection of immune-activating agents into tumors, holds promise for converting immunologically ‘cold’ tumors into responsive ‘hot’ tumors. This review explores the rationale for combining intratumoral therapies (ITs) with ICIs, highlighting their complementary mechanisms of action and clinical effects. Notable IT approaches include oncolytic viruses, toll-like receptor agonists, and stimulator of interferon gene agonists with ICIs. Overall, combining ITs with ICIs offers a rational strategy to potentiate antitumor immune response and overcome resistance. Further research is needed to optimize the combination strategies, identify biomarkers of response, and establish the safety and efficacy of these novel therapeutic approaches.
{"title":"Potentiating intratumoral therapy with immune checkpoint inhibitors: shifting the paradigm of multimodality therapeutics","authors":"B.E. Nelson , A. Naing , S. Fu , R.A. Sheth , R. Murthy , S. Piha-Paul","doi":"10.1016/j.iotech.2024.101040","DOIUrl":"10.1016/j.iotech.2024.101040","url":null,"abstract":"<div><div>Immune checkpoint inhibitors (ICIs) have revolutionized oncology, yielding remarkable and durable responses in various cancers. However, a significant proportion of patients develop resistance to ICIs. The tumor microenvironment plays a critical role in immunotherapy resistance, characterized by immune cell composition, regulatory factors, and tumor mutational burden. Intratumoral immunotherapy, involving direct injection of immune-activating agents into tumors, holds promise for converting immunologically ‘cold’ tumors into responsive ‘hot’ tumors. This review explores the rationale for combining intratumoral therapies (ITs) with ICIs, highlighting their complementary mechanisms of action and clinical effects. Notable IT approaches include oncolytic viruses, toll-like receptor agonists, and stimulator of interferon gene agonists with ICIs. Overall, combining ITs with ICIs offers a rational strategy to potentiate antitumor immune response and overcome resistance. Further research is needed to optimize the combination strategies, identify biomarkers of response, and establish the safety and efficacy of these novel therapeutic approaches.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101040"},"PeriodicalIF":0.0,"publicationDate":"2024-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-04DOI: 10.1016/j.iotech.2024.101031
J. Ma , S. Meyer , J. Olweus , C. Jin , D. Yu
Background
Genetically engineered T-cell therapy holds immense promise in cancer immunotherapy. These T-cell products are typically engineered by vectors that permanently integrate into the T-cell genome, thus raising concerns about potential risks of insertional mutagenesis. Therefore, it becomes imperative to assess the integrated vector copy number (VCN) as a critical safety parameter for gene-engineered cell products.
Materials and methods
In this study, we developed a robust assay for assessing the VCN of chimeric antigen receptor-T cell and T-cell receptor T-cell products, based on the droplet digital polymerase chain reaction (ddPCR) method. To provide accurate representation of the VCN in gene-engineered cells, we implemented a calculation that factors in the putative transduction efficiency based on Poisson distribution statistics. The adjusted VCN value (VCNadj) was also compared with VCN value from sorted transgene-positive cell populations, to validate its accuracy.
Results
This assay consistently and accurately determines the average VCN for cell products. By comparing the VCN in sorted transgene-positive cell populations, we validated the refinement calculation provides a closer approximation to the actual VCN within transduced cells, offering a more realistic representation of the VCN for engineered cell products.
Conclusion
In summary, we present a reliable and robust ddPCR-based assay for quantification of VCN in gene-engineered cell products.
{"title":"An adjusted droplet digital PCR assay for quantification of vector copy number in CAR-T cell and TCR-T cell products","authors":"J. Ma , S. Meyer , J. Olweus , C. Jin , D. Yu","doi":"10.1016/j.iotech.2024.101031","DOIUrl":"10.1016/j.iotech.2024.101031","url":null,"abstract":"<div><h3>Background</h3><div>Genetically engineered T-cell therapy holds immense promise in cancer immunotherapy. These T-cell products are typically engineered by vectors that permanently integrate into the T-cell genome, thus raising concerns about potential risks of insertional mutagenesis. Therefore, it becomes imperative to assess the integrated vector copy number (VCN) as a critical safety parameter for gene-engineered cell products.</div></div><div><h3>Materials and methods</h3><div>In this study, we developed a robust assay for assessing the VCN of chimeric antigen receptor-T cell and T-cell receptor T-cell products, based on the droplet digital polymerase chain reaction (ddPCR) method. To provide accurate representation of the VCN in gene-engineered cells, we implemented a calculation that factors in the putative transduction efficiency based on Poisson distribution statistics. The adjusted VCN value (VCN<sub>adj</sub>) was also compared with VCN value from sorted transgene-positive cell populations, to validate its accuracy.</div></div><div><h3>Results</h3><div>This assay consistently and accurately determines the average VCN for cell products. By comparing the VCN in sorted transgene-positive cell populations, we validated the refinement calculation provides a closer approximation to the actual VCN within transduced cells, offering a more realistic representation of the VCN for engineered cell products.</div></div><div><h3>Conclusion</h3><div>In summary, we present a reliable and robust ddPCR-based assay for quantification of VCN in gene-engineered cell products.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101031"},"PeriodicalIF":0.0,"publicationDate":"2024-12-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-02DOI: 10.1016/j.iotech.2024.101030
J. Palomero , V. Galvao , I. Creus , J. Lostes , M. Aylagas , A. Marín-Bayo , M. Rotxés , M. Sanz , M. Lozano-Rabella , A. Garcia-Garijo , A. Yuste-Estevanez , D. Grases , J. Díaz-Gómez , J. González , J.F. Navarro , J.J. Gartner , I. Braña , X. Villalobos , N. Bayó-Puxan , J. Jiménez , E. Garralda
Background
Adoptive cell therapy (ACT) of ex vivo expanded tumor-infiltrating lymphocytes (TILs) can mediate objective tumor regression in 28%-49% of metastatic melanoma patients. However, the efficacy of TIL therapy in most epithelial cancers remains limited. We present the design of a phase I clinical study that aims to assess the safety and efficacy of NEXTGEN-TIL, a TIL product selected based on ex vivo neoantigen recognition, in patients with advanced epithelial tumors and immune checkpoint blockade (ICB)-resistant solid tumors.
Materials and methods
Pre-rapid expansion protocol (REP) TIL cultures expanded in high-dose interleukin 2 (HD-IL-2) from patients with metastatic solid tumors were screened for recognition of autologous tumor cell lines (TCLs) and/or neoantigens. Six good manufacturing practice (GMP)-grade validations of pre-REP TIL expansion were carried out and TIL cultures from these six intermediate products were selected to carry out the clinical-scale GMP validation of the REP.
Results
TILs expanded in 82% of patient-derived tumor biopsies across different cancer types and these frequently contained tumor- and neoantigen-reactive T cells. During GMP validations, a variable number of TIL cultures expanded, constituting the intermediate products (pre-REP). Three finished products were manufactured using a REP which reached cell doses ranging from 4.3e9 to 1.1e11 and met the established specifications. The NEXTGEN-TIL clinical trial entails a first expansion of TILs from tumor fragments in HD-IL-2 followed by TIL screening for neoantigen recognition and REP of selected neoantigen-reactive TIL cultures. Treatment involves a classical non-myeloablative lymphodepleting chemotherapy followed by NEXTGEN-TIL product administration together with HD-IL-2.
Conclusions
NEXTGEN-TIL exploits ex vivo expanded neoantigen-reactive TIL to potentially improve efficacy in patients with epithelial and ICB-resistant tumors, with a safety profile like traditional TILs.
{"title":"Preclinical data and design of a phase I clinical trial of neoantigen-reactive TILs for advanced epithelial or ICB-resistant solid cancers","authors":"J. Palomero , V. Galvao , I. Creus , J. Lostes , M. Aylagas , A. Marín-Bayo , M. Rotxés , M. Sanz , M. Lozano-Rabella , A. Garcia-Garijo , A. Yuste-Estevanez , D. Grases , J. Díaz-Gómez , J. González , J.F. Navarro , J.J. Gartner , I. Braña , X. Villalobos , N. Bayó-Puxan , J. Jiménez , E. Garralda","doi":"10.1016/j.iotech.2024.101030","DOIUrl":"10.1016/j.iotech.2024.101030","url":null,"abstract":"<div><h3>Background</h3><div>Adoptive cell therapy (ACT) of <em>ex vivo</em> expanded tumor-infiltrating lymphocytes (TILs) can mediate objective tumor regression in 28%-49% of metastatic melanoma patients. However, the efficacy of TIL therapy in most epithelial cancers remains limited. We present the design of a phase I clinical study that aims to assess the safety and efficacy of NEXTGEN-TIL, a TIL product selected based on <em>ex vivo</em> neoantigen recognition, in patients with advanced epithelial tumors and immune checkpoint blockade (ICB)-resistant solid tumors.</div></div><div><h3>Materials and methods</h3><div>Pre-rapid expansion protocol (REP) TIL cultures expanded in high-dose interleukin 2 (HD-IL-2) from patients with metastatic solid tumors were screened for recognition of autologous tumor cell lines (TCLs) and/or neoantigens. Six good manufacturing practice (GMP)-grade validations of pre-REP TIL expansion were carried out and TIL cultures from these six intermediate products were selected to carry out the clinical-scale GMP validation of the REP.</div></div><div><h3>Results</h3><div>TILs expanded in 82% of patient-derived tumor biopsies across different cancer types and these frequently contained tumor- and neoantigen-reactive T cells. During GMP validations, a variable number of TIL cultures expanded, constituting the intermediate products (pre-REP). Three finished products were manufactured using a REP which reached cell doses ranging from 4.3e9 to 1.1e11 and met the established specifications. The NEXTGEN-TIL clinical trial entails a first expansion of TILs from tumor fragments in HD-IL-2 followed by TIL screening for neoantigen recognition and REP of selected neoantigen-reactive TIL cultures. Treatment involves a classical non-myeloablative lymphodepleting chemotherapy followed by NEXTGEN-TIL product administration together with HD-IL-2.</div></div><div><h3>Conclusions</h3><div>NEXTGEN-TIL exploits ex vivo expanded neoantigen-reactive TIL to potentially improve efficacy in patients with epithelial and ICB-resistant tumors, with a safety profile like traditional TILs.</div></div>","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"25 ","pages":"Article 101030"},"PeriodicalIF":0.0,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143155987","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.iotech.2024.100900
H.J. Kim , B.K. Jung , L.K. Kim , S-A. Park , T-H. Heo
{"title":"17P Identification PD-L1-associated lncRNA biomarkers for immunoregulation in ovarian cancer","authors":"H.J. Kim , B.K. Jung , L.K. Kim , S-A. Park , T-H. Heo","doi":"10.1016/j.iotech.2024.100900","DOIUrl":"10.1016/j.iotech.2024.100900","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100900"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143176151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.iotech.2024.100885
T. Hakozaki , K. Tanaka , Y. Shiraishi , Y. Sekino , N. Mitome , Y. Okuma , T. Aiba , T. Utsumi , J. Tanizaki , K. Azuma , S. Hara , R. Morita , S. Niho , T. Yokoyama , R. Toyozawa , H. Horinouchi , I. Okamoto , Y. Hosomi , Y. Ohe
{"title":"1O Exploration of gut microbiota biomarkers in treatment-naïve advanced NSCLC patients undergoing chemo-immunotherapy: Insights from the phase III trial, JCOG2007 (NIPPON)","authors":"T. Hakozaki , K. Tanaka , Y. Shiraishi , Y. Sekino , N. Mitome , Y. Okuma , T. Aiba , T. Utsumi , J. Tanizaki , K. Azuma , S. Hara , R. Morita , S. Niho , T. Yokoyama , R. Toyozawa , H. Horinouchi , I. Okamoto , Y. Hosomi , Y. Ohe","doi":"10.1016/j.iotech.2024.100885","DOIUrl":"10.1016/j.iotech.2024.100885","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100885"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143177797","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.iotech.2024.100870
N. Mach , E. Fernandez , R. Vernet , M. Urwyler , O. von Rohr , E. Charrier , M-C. Belkouch , V. Saingier , F. Courtout , C. de Vito , V. Ancrenaz , N. Dulguerov , W. Karenovics , J. Grogg , J. Renaux , T. Brezina , T. Rordorf , M. Joerger , O.A. Michielin , J. Villard
{"title":"59P Long term survival data from all recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) patients treated with MVX-ONCO-1 during open-labelled phase I and phase IIa clinical trials","authors":"N. Mach , E. Fernandez , R. Vernet , M. Urwyler , O. von Rohr , E. Charrier , M-C. Belkouch , V. Saingier , F. Courtout , C. de Vito , V. Ancrenaz , N. Dulguerov , W. Karenovics , J. Grogg , J. Renaux , T. Brezina , T. Rordorf , M. Joerger , O.A. Michielin , J. Villard","doi":"10.1016/j.iotech.2024.100870","DOIUrl":"10.1016/j.iotech.2024.100870","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100870"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.iotech.2024.100920
E.M. Bob , C.C. Burz
{"title":"38P Biomarkers predictive of response to immune checkpoint inhibitor therapy in patients with metastatic melanoma","authors":"E.M. Bob , C.C. Burz","doi":"10.1016/j.iotech.2024.100920","DOIUrl":"10.1016/j.iotech.2024.100920","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100920"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143128833","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-12-01DOI: 10.1016/j.iotech.2024.100825
Z. Zhang , K. Yang , S. Zhao , Z. Yang , Z. Xiong
{"title":"82P Predictive biomarkers for neoadjuvant immunochemotherapy efficacy in locally advanced cancer patients: A retrospective analysis based on changes in tumor shrinkage rate and lymphocyte count","authors":"Z. Zhang , K. Yang , S. Zhao , Z. Yang , Z. Xiong","doi":"10.1016/j.iotech.2024.100825","DOIUrl":"10.1016/j.iotech.2024.100825","url":null,"abstract":"","PeriodicalId":73352,"journal":{"name":"Immuno-oncology technology","volume":"24 ","pages":"Article 100825"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143129135","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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