scholarly journals Multi-functional cytotoxic T cell expansion correlates with overall survival after administration of autologous dendritic cell immunotherapy in renal cell cancer patients

2013 ◽  
Vol 1 (S1) ◽  
Author(s):  
M DeBenedette ◽  
I Jurisica ◽  
A Gamble ◽  
W Lewis ◽  
E Wansley ◽  
...  
Keyword(s):  
Overall Survival ◽  
T Cell ◽  
Dendritic Cell ◽  
Cancer Patients ◽  
Renal Cell ◽  
Cell Expansion ◽  
Cell Cancer ◽  
Cytotoxic T Cell ◽  
Autologous Dendritic Cell ◽  
Cell Immunotherapy

Toxicities of axitinib, sunitinib and temsirolimus: implications for progression-free and overall survival in metastatic renal cell cancer

2020 ◽  
Author(s):  
Annemarie Uhlig ◽  
Johannes Uhlig ◽  
Lutz Trojan ◽  
Michael Woike ◽  
Marianne Leitsmann ◽  
...  
Keyword(s):  
Overall Survival ◽  
Cancer Patients ◽  
Skin Reaction ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Cox Models ◽  
Metastatic Renal Cell Cancer ◽  
Hand Foot Skin Reaction

The aim of this study was to evaluate the association between axitinib, sunitinib and temsirolimus toxicities and patient survival in metastatic renal cell cancer patients. Overall survival (OS) and progression-free survival (PFS) of metastatic renal cell cancer patients from the prospective multicenter STAR-TOR study were assessed using multivariable Cox models. A total of 1195 patients were included (n = 149 axitinib; n = 546 sunitinib; n = 500 temsirolimus). The following toxicities significantly predicted outcomes: hand–foot skin reaction (hazard ratio [HR] = 0.29) for PFS with axitinib; stomatitis (HR = 0.62) and pneumonitis (HR = 0.23) for PFS with temsirolimus; stomatitis (HR = 0.52) and thrombocytopenia (HR = 0.6) for OS with temsirolimus; fatigue (HR = 0.71) for PFS with sunitinib; hand–foot skin reaction (HR = 0.56) and fatigue (HR = 0.58) for OS with sunitinib. In conclusion, in metastatic renal cell cancer, axitinib, sunitinib and temsirolimus demonstrate specific toxicities that are protective OS/PFS predictors.

Identification of multifunctional cytotoxic T-cell subsets as immune correlates with clinical outcomes in a phase II study of AGS-003, an autologous dendritic cell-based therapy administered to patients with newly diagnosed, metastatic RCC.

2012 ◽  
Vol 30 (30_suppl) ◽  
pp. 80-80 ◽  
Author(s):  
Mark DeBenedette ◽  
Igor Jurisica ◽  
Alicia H. Gamble ◽  
Irina Y. Tcherepanova ◽  
W. Lee Williams ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
Clinical Outcome ◽  
Phase Ii ◽  
Expression Patterns ◽  
Phase Iii ◽  
Cytotoxic T Cell ◽  
Newly Diagnosed ◽  
Autologous Dendritic Cell ◽  
Combinatorial Expression

80 Background: AGS-003 is an autologous dendritic cell (DC) immunotherapy prepared from matured monocyte-derived DC co-electroporated with the subject’s own amplified tumor RNA and synthetic CD40L RNA. The mechanism of action (MOA) of AGS-003 was evaluated in combination with sunitinib for treatment of advanced renal cell carcinoma (RCC) in AGS-003-006, an open label phase II trial including subjects with newly diagnosed, unfavorable-risk, metastatic clear cell RCC. The goal of the immune monitoring platform is to identify unique cytotoxic T-cell (CTL) signatures that correlate with clinical outcome in subjects receiving AGS-003 in combination with sunitinib. Methods: Multiparametric flow cytometry was used to identify tumor-reactive CTL subsets induced by AGS-003 based on combinatorial expression patterns of surface markers CD28, CD45RA, CD27 and CCR7. Moreover, further partitioning of each CTL subset identified combinatorial expression patterns of Markers of Immune Function (MIFs) defined as cytokines (IFN-γ TNF-α, IL-2), cytolytic markers (Granzyme b, CD107) and proliferation. Correlates of CTL signatures with clinical outcome were analyzed using an adaptation of a binary tree-structured vector quantization (BTSVQ) approach, originally developed to cluster and visualize large microarray data sets. The BTSVQ approach implements a two-way unsupervised clustering that allows a subject’s CTL signature to be mapped based on both surface marker and MIFs expression patterns to identify unique clustering patterns linked to clinical outcome. Results: Data analysis identified a unique CTL signature (CD28+/CCR7+/CD45RA- phenotype) displaying a broad MIFs profile as a statistically significant correlate to PFS and OS in patients treated with AGS-003. Conclusions: These results support the intended MOA of AGS-003 in vivo, as the induction of anti-tumor central and effector memory CTL responses. These data warrant further immunological evaluation of AGS-003 in the randomized phase III ADAPT study using AGS-003 in combination with standard treatment in RCC subjects.

CD40 ligand is essential for generation of specific cytotoxic T cell responses in RNA-pulsed dendritic cell immunotherapy

Surgery ◽  
2003 ◽  
Vol 134 (2) ◽  
pp. 300-305 ◽  
Author(s):  
Mark W. Onaitis ◽  
Matthew F. Kalady ◽  
Sirisha Emani ◽  
Zeinab Abdel-Wahab ◽  
Douglas S. Tyler ◽  
...  
Keyword(s):  
T Cell ◽  
Dendritic Cell ◽  
T Cell Responses ◽  
Cd40 Ligand ◽  
Cytotoxic T Cell ◽  
Cell Responses ◽  
Cell Immunotherapy ◽  
Cytotoxic T Cell Responses

scholarly journals Sunitinib-Induced Myeloid Lineage Redistribution in Renal Cell Cancer Patients: CD1c+ Dendritic Cell Frequency Predicts Progression-Free Survival

2008 ◽  
Vol 14 (18) ◽  
pp. 5884-5892 ◽  
Author(s):  
Hester van Cruijsen ◽  
Astrid A.M. van der Veldt ◽  
Laura Vroling ◽  
Dinja Oosterhoff ◽  
Henk J. Broxterman ◽  
...  
Keyword(s):  
Dendritic Cell ◽  
Cancer Patients ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Progression Free Survival ◽  
Cell Frequency ◽  
Myeloid Lineage ◽  
Free Survival

Plasma MN (carbonic anhydrase IX) and outcome in sunitinib-treated metastatic renal cell cancer.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 405-405
Author(s):  
Nicholas E. Lamparella ◽  
Suhail M. Ali ◽  
Kim Leitzel ◽  
Walter P. Carney ◽  
Allan Lipton
Keyword(s):  
Overall Survival ◽  
Multivariate Analysis ◽  
Carbonic Anhydrase ◽  
Cancer Patients ◽  
Renal Cell Cancer ◽  
Renal Cell ◽  
Cell Cancer ◽  
Carbonic Anhydrase Ix ◽  
Lower Plasma ◽  
Metastatic Renal Cell Cancer

405 Background: The transmembrane protein MN (carbonic anhydrase IX)(CAIX) catalyzes the hydration of carbon dioxide to carbonic acid and decreases pH. In cancer, up-regulation of CAIX gene expression occurs under hypoxic conditions within tumors. Significant levels of CAIX protein have been detected in a variety of cancers including kidney, cervix, lung, bladder, colon, breast, liver, gall bladder, and pancreas. Methods: Pretreatment plasma CAIX and VEGF-A levels were determined from 52 metastatic renal cell cancer patients enrolled in a phase III first-line trial of sunitinib vs. interferon alpha (IF). The CAIX and VEGF-A ELISAs (WILEX/Oncogene Science, Cambridge MA) were used for determination of plasma biomarker levels. 51 of 52 patients had an MSKCC score of 0 or 1. Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method and Cox modeling with both continuous and dichotomous (median) plasma CAIX and VEGF levels. Results: Pretreatment plasma CAIX levels averaged 371 pg/ml, with a median of 194 pg/ml and 25th and 75th percentile values of 125 and 298 pg/ml, respectively. In the whole population, higher plasma CAIX was significant on a continuous basis for predicting reduced PFS (p < 0.007) and shorter OS (p <0.0001). When analyzed using the median as cutpoint, the elevated plasma CAIX cohort trended for reduced PFS (p = 0. 13) and had a significantly reduced OS (HR 2.77, p = 0.026) (median 94 vs. 115 weeks). In univariate analysis plasma VEGF-A did not predict for PFS or OS when analyzed as a continuous or dichotomous variable. In multivariate analysis for PFS (including treatment arm, CAIX, and MSKCC score), treatment with sunitinib (vs. IF) (p = 0.006) and lower plasma CAIX (p = 0.04) resulted in a significantly longer PFS. In multivariate analysis for OS, again treatment with sunitinib (vs. IF) (p=0.037), and lower plasma CAIX (p < 0.0001) resulted in a significantly longer OS. Conclusions: Elevated pretreatment plasma CAIX predicted for reduced PFS and overall survival in metastatic renal cancer patients. In addition, sunitinib was superior to interferon, regardless of plasma CAIX status.

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