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Dendritic Cell Vaccines for Gliomas 97 MALIGNANT GLIOMA RESPONSIVENESS TO CHEMOTHERAPY POST-DC VACCINATION The processes that can explain a reason why tumor recurs despite CTL induction by DC vaccination are immunoselection and immunoediting. These processes allow tumor cells to escape from CTLs by antigen loss (65,66). The potential synergies between immunotherapy and other therapies must therefore be investigated due to the clinical inconsistency of cancer vaccines and the effects of immunoselection on tumor evolution (67–69). Cedars-Sinai Medical Center (68) and Brigham and Women’s Hospital have conducted clinical trials to examine the synergy of vaccines with chemotherapy treatment (70). A retrospective analysis of clinical outcomes (survival and progression times) in 25 vaccinated (13 with and 12 without subsequent chemotherapy) and 13 nonvaccinated de novo GBM patients receiving chemotherapy was performed. Patients who received post-vaccine chemotherapy demonstrated longer survival times and significantly longer times to tumor recurrence after chemotherapy relative to their own previous recurrence times, as well as to patients receiving vaccine or chemotherapy alone (Fig. 5). Two of these patients who underwent Figure 5 Overall survival in vaccine, chemotherapy, and vaccine + chemotherapy groups. Overall survival was defined as the time from first diagnosis of brain tumor (de novo GBM in all cases) to death due to tumor progression. Kaplan-Meier survival plots with censored values in open circles are shown for each group. Survival of the vaccine group was identical to that of chemotherapy group (P ¼ 0.7, log-rank test). Survival of vaccine + chemotherapy group was significantly greater relative to survival in the other two groups together (P ¼ 0.048, log-rank test), greater than survival in the chemotherapy group alone (P ¼ 0.028, log-rank test), and greater than survival in the vaccine group alone (P ¼ 0.048, log-rank test). Two of the three patients exhibiting objective tumor regression survived for >2 years (730 days) after diagnosis. (Reproduced from Wheeler CJ. et al. Clinical Cancer Research, 2004, 10(16): 5316–5326)
98 Luptrawan et al. Figure 6 Tumor regression following post-vaccine chemotherapy. Relative days after diagnosis are represented by the numbers under individual MRI scans, with individual patient scans in each row. Patient 11 recurred 82 days after vaccine initiation; patient 9 recurred 147 days after vaccine initiation, was treated surgically, and recurred 227 additional days (374 days total) after vaccine initiation. (Reproduced from Wheeler CJ. et al. Clinical Cancer Research, 2004, 10(16): 5316–5326) treatment with temozolomide after recurrence demonstrated a dramatic response (Fig. 6). DC vaccination works in synergy with subsequent chemotherapy to elicit tangible clinical benefits for GBM patients. This is based on the evidence that DC vaccination induces specific CTL targeting of drug resistance–related TAAs and clinical observations. The results of these recent clinical trials strongly support the concept of utilization of DC immunotherapy to sensitize tumor cells to chemotherapy. FUTURE STRATEGIES FOR DC VACCINES The success of vaccines depends on the identification of appropriate tumor antigens, establishment of effective immunization strategies, and their ability to circumvent inhibitory immune mechanisms. The challenge for scientists in the future will be to further extend our fundamental knowledge of DC immunobiology, tumor immunology, and cancer biology, and to implement these findings in the rational design of DC immunotherapy for the treatment of cancer patients.
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Translational Medicine Series 6 Can
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TRANSLATIONAL MEDICINE SERIES 1. Pr
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Informa Healthcare USA, Inc. 52 Van
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Preface Throughout the last 20 year
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Preface vii Table 1 A Diverse Techn
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Preface . . . . v Contributors . .
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Contributors Pedro Alves Ludwig Ins
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1 Factoring in Antigen Processing i
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Factoring in Antigen Processing in
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2 Outlining the Gap Between Preclin
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Preclinical Models and Clinical Sit
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Table 1 Examples of Preclinical Act
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Figure 5.1 Immunohistochemical char
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Figure 8.5 A schematic representati
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Multimodality Immunization Approach
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Multimodality Immunization Approach
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8 Bidirectional Bedside Lab Bench P
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Development of Novel Immunotherapeu
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206 Index Antigenic peptides degrad
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208 Index Chromogens, enzymatic act
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210 Index Freund’s adjuvants. See
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212 Index Langerhans cells, 133, 13
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214 Index [Peptide vaccines] invest
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216 Index TCRL. See TCR-like immuno
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Oncology and Immunology about the b
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