Biological activities of a recombinant adenovirus p53 (SCH 58500) administered by hepatic arterial infusion in a Phase 1 colorectal cancer trial

Atencio, Isabella A.; Grace, Michael J.; Bordens, Ronald; Fritz, Mary Ann; Horowitz, Jo Ann; Hutchins, Beth; Indelicato, Stephen R.; Jacobs, S C; Kolz, Karen; Maneval, Daniel C.; Musco, Mary Lynn; Shinoda, Jeremy; Venook, Alan P.; Wen, Sijian; Warren, Robert S.

doi:10.1038/sj.cgt.7700870

Cited by 45 publications

(25 citation statements)

References 34 publications

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“…In another trial with an Ad p53 vector (SCH 58500) similar to Advexin, patients receiving 7.5 × 10 13 vp of vector intraarterially developed a strong innate and adaptive immune response to the vector, but no serious adverse events were reported [37]. …”

Section: Clinical Experience With Advexin and Gendicine Two Rd Admentioning

confidence: 99%

Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

Wold¹,

Tóth²

2014

CGT

457

359

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Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vectors are engineered to replicate preferentially in cancer cells and to destroy cancer cells through the natural process of lytic virus replication. Many clinical trials indicate that replication-defective and replication-competent adenovirus vectors are safe and have therapeutic activity.

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Section: Clinical Experience With Advexin and Gendicine Two Rd Admentioning

confidence: 99%

Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

Wold¹,

Tóth²

2014

CGT

457

359

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“…The OTC trial was further compromised by problems in the design and conduct of the trial, as acknowledged and fully detailed by the trial’s Principal Investigator (Wilson, 2009). To be clear, there have been subsequent human trials to the OTC trial, that have also intravascularly administered (in a similar fashion to the OTC trial) equivalent, or even higher doses of Ad-based vectors to large numbers of trial subjects, and not had the unfortunate outcome reported in the 1999 OTC trial (Atencio et al, 2006). The reasons for this dichotomy in responses are numerous, and likely may never be resolved (Wilson, 2009).…”

Section: Introductionmentioning

confidence: 99%

Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm

Aldhamen¹,

Seregin²,

Amalfitano³

2011

Front. Immun.

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Recombinant Adenovirus (Ad) based vectors have been utilized extensively as a gene transfer platform in multiple pre-clinical and clinical applications. These applications are numerous, and inclusive of both gene therapy and vaccine based approaches to human or animal diseases. The widespread utilization of these vectors in both animal models, as well as numerous human clinical trials (Ad-based vectors surpass all other gene transfer vectors relative to numbers of patients treated, as well as number of clinical trials overall), has shed light on how this virus vector interacts with both the innate and adaptive immune systems. The ability to generate and administer large amounts of this vector likely contributes not only to their ability to allow for highly efficient gene transfer, but also their elicitation of host immune responses to the vector and/or the transgene the vector expresses in vivo. These facts, coupled with utilization of several models that allow for full detection of these responses has predicted several observations made in human trials, an important point as lack of similar capabilities by other vector systems may prevent detection of such responses until only after human trials are initiated. Finally, induction of innate or adaptive immune responses by Ad vectors may be detrimental in one setting (i.e., gene therapy) and be entirely beneficial in another (i.e., prophylactic or therapeutic vaccine based applications). Herein, we review the current understanding of innate and adaptive immune responses to Ad vectors, as well some recent advances that attempt to capitalize on this understanding so as to further broaden the safe and efficient use of Ad-based gene transfer therapies in general.

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“…Although these results seem promising, the safety limitations of the retroviral vector system shifted the focus of p53-based gene therapy to other vectors. Most of the subsequent trials used adenoviral vectors SCH58500 or INGN201 containing a WT p53 transgene 128, 129, 130, 131, 132, 133, 134, 135, 136, 137. Both SCH58500 (Schering-Plough) and INGN201 (also known as Advexin; Introgen Therapeutics) contain a WT p53 expression cassette in place of the Ad E1 region, with WT p53 gene under the control of the human cytomegalovirus promoter.…”

Section: Main Textmentioning

confidence: 99%

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

Bressy

Hastie

Grdzelishvili

2017

Molecular Therapy - Oncolytics

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Oncolytic virus (OV) therapy utilizes replication-competent viruses to kill cancer cells, leaving non-malignant cells unharmed. With the first U.S. Food and Drug Administration-approved OV, dozens of clinical trials ongoing, and an abundance of translational research in the field, OV therapy is poised to be one of the leading treatments for cancer. A number of recombinant OVs expressing a transgene for p53 (TP53) or another p53 family member (TP63 or TP73) were engineered with the goal of generating more potent OVs that function synergistically with host immunity and/or other therapies to reduce or eliminate tumor burden. Such transgenes have proven effective at improving OV therapies, and basic research has shown mechanisms of p53-mediated enhancement of OV therapy, provided optimized p53 transgenes, explored drug-OV combinational treatments, and challenged canonical roles for p53 in virus-host interactions and tumor suppression. This review summarizes studies combining p53 gene therapy with replication-competent OV therapy, reviews preclinical and clinical studies with replication-deficient gene therapy vectors expressing p53 transgene, examines how wild-type p53 and p53 modifications affect OV replication and anti-tumor effects of OV therapy, and explores future directions for rational design of OV therapy combined with p53 gene therapy.

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Biological activities of a recombinant adenovirus p53 (SCH 58500) administered by hepatic arterial infusion in a Phase 1 colorectal cancer trial

Cited by 45 publications

References 34 publications

Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

Immune Recognition of Gene Transfer Vectors: Focus on Adenovirus as a Paradigm

Combining Oncolytic Virotherapy with p53 Tumor Suppressor Gene Therapy

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