2015
DOI: 10.1007/s00262-015-1706-4
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Extended evaluation of a phase 1/2 trial on dosing, safety, immunogenicity, and overall survival after immunizations with an advanced-generation Ad5 [E1-, E2b-]-CEA(6D) vaccine in late-stage colorectal cancer

Abstract: A phase 1/2 clinical trial evaluating dosing, safety, immunogenicity, and overall survival on metastatic colorectal cancer (mCRC) patients after immunotherapy with an advanced generation Ad5 [E1-, E2b-]-CEA(6D) vaccine was performed. We report our extended observations on long-term overall survival and further immune analyses on a subset of treated patients including assessment of cytolytic T cell responses, T-regulatory (Treg) to T-effector (Teff) cell ratios, flow cytometry on peripheral blood mononuclear ce… Show more

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Cited by 46 publications
(38 citation statements)
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“…A contemporary control group displayed identical time to progression as the vaccinated group, but OS was approximately 50% at 4 y, which is comparable to other reported studies in this population. 10,11 An adenovirus-CEA vaccine 12 and an MVA-5T4 (TroVax) vaccine 13 also reported some evidence of clinical benefit in patients with advanced mCRC. While very few RECIST responses have been observed in non-MSI mCRC patients treated with MAbs directed against the checkpoint inhibitors anti-PD1/PDL1, several patients have shown long-term stable disease post-therapy.…”
Section: Discussionmentioning
confidence: 99%
“…A contemporary control group displayed identical time to progression as the vaccinated group, but OS was approximately 50% at 4 y, which is comparable to other reported studies in this population. 10,11 An adenovirus-CEA vaccine 12 and an MVA-5T4 (TroVax) vaccine 13 also reported some evidence of clinical benefit in patients with advanced mCRC. While very few RECIST responses have been observed in non-MSI mCRC patients treated with MAbs directed against the checkpoint inhibitors anti-PD1/PDL1, several patients have shown long-term stable disease post-therapy.…”
Section: Discussionmentioning
confidence: 99%
“…This limitation has been overcome by engineered adenoviruses which are capable of safely vaccinating and re-vaccinating against hundreds of neoepitopes and tumor associated antigens despite pre-existing immunity against adenoviruses [139]. Remarkable results have thus far been published demonstrating the delivery of tumor-associated antigens by engineered adenoviruses in a cohort of late-stage colorectal cancer patients [140].…”
Section: H a View To The Future: A Truly "N=1"-medicinementioning
confidence: 99%
“…Many TAAs are in a tolerised state with respect to the immune system amongst patients, requiring potent stimulation to disrupt tolerance. Therapeutic vaccine approaches for CRC can overcome this through the use of viral vectors, such as adenovirus [ 3 ], alphavirus [ 4 ], and vaccinia [ 5 ]; however, each of these vaccines possess specific design flaws that may impair their overall efficacy. These therapies target a single antigen, such as carcinoembryonic antigen (CEA), a TAA normally found expressed at low levels throughout the intestinal mucosa [ 6 ] and overexpressed in the majority of adenocarcinomas originating in either the colon or rectum [ 7 ].…”
Section: Introductionmentioning
confidence: 99%