Phase II trial of Modified Vaccinia Ankara (MVA) virus expressing 5T4 and high dose Interleukin-2 (IL-2) in patients with metastatic renal cell carcinoma

Kaufman, Howard L.; Taback, Bret; Sherman, William H.; Kim, Dae Won; Shingler, William; Moroziewicz, Dorota; DeRaffele, Gail; Mitcham, Josephine; Carroll, Miles W.; Harrop, Richard; Naylor, Stuart; Kim‐Schulze, Seunghee

doi:10.1186/1479-5876-7-2

Cited by 68 publications

(52 citation statements)

References 28 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Results from phase I and II clinical studies of MVA-5T4 in renal, colorectal, and prostate cancer patients were encouraging and showed that immune responses were induced in almost all treated patients, and associations between 5T4-specific cellular or humoral responses and clinical benefit were reported in seven of nine studies (8)(9)(10)(11)(12)(13)(14)(15)(16). In particular, studies in RCC and colorectal cancer patients have detected an association between 5T4-specific (but not MVA) antibody responses and enhanced survival (9,12,16).…”

Section: Discussionmentioning

confidence: 88%

“…Previous data from phase II studies in RCC patients treated with MVA-5T4 and IL-2 also showed encouraging signs of clinical benefit (13,16). Currently, it is unclear why a survival advantage in patients with an intermediate prognosis treated with MVA-5T4 plus IL-2 was not seen.…”

Section: Discussionmentioning

confidence: 97%

“…These studies showed MVA-5T4 to be well tolerated and able to induce 5T4-specific immune responses in most patients. Furthermore, associations between 5T4-specific cellular or humoral responses and clinical benefit were reported in seven of the nine studies (8)(9)(10)(11)(12)(13)(14)(15)(16).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Vaccination of Metastatic Renal Cancer Patients with MVA-5T4: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

Amato

Hawkins

Kaufman

et al. 2010

Clinical Cancer Research

Self Cite

186

119

View full text Add to dashboard Cite

Purpose: The TroVax Renal Immunotherapy Survival Trial was a randomized, placebo-controlled phase III study that investigated whether modified vaccinia Ankara encoding the tumor antigen 5T4 (MVA-5T4) prolonged survival of patients receiving first-line standard-of-care (SOC) treatment for metastatic renal cell cancer.Experimental Design: Patients with metastatic clear cell renal cancer, prior nephrectomy, and good or intermediate prognosis were randomized 1:1 to receive up to 13 immunizations of MVA-5T4/placebo in combination with either sunitinib, interleukin-2 or interferon-α. The primary end point was overall survival. Secondary end points included progression-free survival, overall response rate, and safety.

show abstract

Section: Discussionmentioning

confidence: 88%

Section: Discussionmentioning

confidence: 97%

See 1 more Smart Citation

Vaccination of Metastatic Renal Cancer Patients with MVA-5T4: A Randomized, Double-Blind, Placebo-Controlled Phase III Study

Amato

Hawkins

Kaufman

et al. 2010

Clinical Cancer Research

Self Cite

186

119

View full text Add to dashboard Cite

show abstract

“…Based on this understanding, current development of novel oncolytic vectors focuses not only on enhancing lytic replication, but also on harnessing the immune response, for example by the introduction of transgenes encoding cytokines [96,97], checkpoint inhibitors [98], ligands of T cell co-stimulatory receptors [99], bispecific T cell engagers [100][101][102] or tumor antigens [103][104][105], respectively, into the viral backbone. Combination therapies represent another approach to support immune responses to OV treatment, including additional application of cytokines [106], immune checkpoint inhibitors [107,108] or chemotherapeutics [109].…”

Section: Modes Of Action In Oncolytic Virotherapymentioning

confidence: 99%

Fighting Cancer with Mathematics and Viruses

Santiago¹,

Heidbuechel²,

Kandell³

et al. 2017

Preprint

View full text Add to dashboard Cite

After decades of research, oncolytic virotherapy has recently advanced to clinical application, and currently a multitude of novel agents and combination treatments are being evaluated for cancer therapy. Oncolytic agents preferentially replicate in tumor cells, inducing tumor cell lysis and complex anti-tumor effects, such as innate and adaptive immune responses and the destruction of tumor vasculature. With the availability of different vector platforms and the potential of both genetic engineering and combination regimens to enhance particular aspects of safety and efficacy, the identification of optimal treatments for patient subpopulations or even individual patients becomes a top priority. Mathematical modeling can provide support in this arena by making use of experimental and clinical data to generate hypotheses about the mechanisms underlying complex biology and, ultimately, predict optimal treatment protocols. Increasingly complex models can be applied to account for therapeutically relevant parameters such as components of the immune system. In this review, we describe current developments in oncolytic virotherapy and mathematical modeling to discuss the benefit of integrating different modeling approaches into biological and clinical experimentation. Conclusively, we propose a mutual combination of these fields of research for more efficient development and effective treatments.

show abstract

“…In a high-dose study in which patients received MVA-5T4 injections at three-week intervals along with 600,000IU/kg interleukin 2 at weeks three, six, nine, and 12 (Kaufman, Taback, Sherman, et al, 2009). The results attributed a large number of adverse events to high-dose interleukin 2, but only two events (grade I fevers) to MVA-5T4, indicating that the regimen is safe and well tolerated in this population of patients.…”

Section: Viral Vector-based Immunotherapymentioning

confidence: 99%