Treatment of mesothelioma with gene-modified PA1STK cells and ganciclovir: a phase I study

Schwarzenberger, Paul; Byrne, P. S.; Gaumer, Richard; Norton, J A; Harrison, Lynn H.; Marrogi, Aizen J.; Kolls, Jay K.

doi:10.1038/cgt.2011.60

Cited by 13 publications

(9 citation statements)

References 17 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The earliest intrapleural cellular immunotherapies involved the delivery of genetically modified allogeneic ovarian carcinoma cells engineered to express the herpes simplex virus thymidine kinase gene (HSVtk) in combination with systemic ganciclovir (gene‐modified PA1‐STK cells) . While not initially designed to be an immunotherapy protocol per se, the generation of antitumor immune responses has been determined to be a key mechanism of action of intrapleural gene‐modified PA1‐STK cells . Induced immune responses may have developed against mesothelin, which is present on both the cell surfaces of the gene‐modified PA1‐STK cells and MPM cells within the involved pleural space.…”

Section: Intrapleural Cellular Immunotherapymentioning

confidence: 99%

“…Induced immune responses may have developed against mesothelin, which is present on both the cell surfaces of the gene‐modified PA1‐STK cells and MPM cells within the involved pleural space. In a phase I clinical trial of intrapleural delivery of gene‐modified PA1‐STK cells followed by 7 days of intravenous ganciclovir infusion in MPM, treatment was overall well tolerated and robust increases in pleural and serum Th1 and Th2 cytokines after treatment were observed …”

Section: Intrapleural Cellular Immunotherapymentioning

confidence: 99%

See 1 more Smart Citation

Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy

Murthy¹,

Katzman²,

Sterman³

2019

Clinical Respiratory J

View full text Add to dashboard Cite

Objectives Malignant pleural mesothelioma and malignant pleural effusions are a major therapeutic challenge, and are associated with impairment in quality of life and increased mortality. Advances in systemic therapies of malignant pleural mesothelioma have demonstrated limited clinical benefit and there is ongoing interest in intrapleural immunotherapies which have been demonstrated to be well tolerated overall with variable clinical responses. We have reviewed the literature to provide a comprehensive summary of novel intrapleural immunotherapeutic paradigms, including oncolytic virus therapy, gene‐mediated cytotoxic immunotherapy, direct cytokine‐mediated immunotherapies, innate immunomodulators and adoptive transfer of intrapleural chimeric antigen receptor T‐cell therapy. Data sources A review of PubMed for original manuscripts and conference reports published between 1998 and 2018 pertaining to intrapleural immunotherapy, as well as examination of reference lists from reviewed manuscripts. Study selection Human clinical trials on intrapleural immunotherapies in subjects with malignant pleural mesothelioma or malignant pleural effusion were included in this review, including some relevant preclinical studies and anticipated ongoing trials reported on Clinicaltrials.gov. Results Twenty‐six clinical trials were identified, in addition to three trials currently in progress. Conclusion Intrapleural immunotherapies for pleural malignancy have demonstrated promise with regard to generating durable tumor‐specific immune responses with possible clinical benefits which merit further investigation as part of multimodal chemotherapeutic and immunotherapeutic regimens.

show abstract

Section: Intrapleural Cellular Immunotherapymentioning

confidence: 99%

Section: Intrapleural Cellular Immunotherapymentioning

confidence: 99%

Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy

Murthy¹,

Katzman²,

Sterman³

2019

Clinical Respiratory J

View full text Add to dashboard Cite

show abstract

“…In the presence of ganciclovir, CCL5-HSV-TK engineered MSCs led not only to a significant reduction in the growth of primary pancreatic tumors, but also dramatically reduced the incidence of metastases [49]. A direct comparison of the Tie2 and CCL5 targeting strategies in an orthotopic model of hepatocellular carcinoma showed that while both approaches suppress tumor growth, the CCL5 strategy was more effective [50]. We believe that based on the unique biology of each tumor type, each tumor entity will be more or less susceptible to a specific targeting approach.…”

Section: Tissue Specific Promoters Allow Selective Delivery Of Therapmentioning

confidence: 99%

Suicide Gene Therapy against Cancer

Rajab¹,

Nelson²

2013

J Genet Syndr Gene Ther

View full text Add to dashboard Cite

A major limitation of conventional chemotherapies used in cancer treatments today are low therapeutic indices and side effects that result from drug effects on normal tissues (off target). One of the most innovative approaches to developing antineoplastic agents with increased tumor selectivity is the use of suicide gene therapy. Suicide gene therapy involves delivering a gene product in proximity to the targeted cancer tissue through various targeted delivery methods followed by tissue/tumor-specific expression of the gene product which then converts a systemically available pro-drug into an active drug within the tumor locale. Here we summarize the concept of gene therapy for cancer and introduce the most frequently used suicide gene therapy systems. In addition we discuss viral, molecular and cellular vectors and their advantages and disadvantages. Finally, we describe the clinical applications, limitations and potential side effects of suicide gene therapy to date.

show abstract

“…Based on these studies, a cell-transfer trial was conducted by Schwarzenberger et al [61] at the Louisiana State University (LSU) Medical Center in New Orleans. The study was a phase I clinical trial involving direct IP infusion of escalating doses of HSVtk suicide gene-modified PA1STK cells in 15 patients with MM followed by 7 days of intravenous GCV.…”

Section: Vectors Used In Pleural Gene Therapymentioning

confidence: 99%

“…No significant differences were seen between serum and pleura cytokine profiles, with the exception of IL-10, which was consistently elevated in the pleural fluid specimens. No objective radiographic responses were observed in any of the treated patients [61]. …”

Section: Vectors Used In Pleural Gene Therapymentioning

confidence: 99%

Novel Intrapleural Therapies for Malignant Diseases

Haas¹,

Sterman²

2012

Respiration

View full text Add to dashboard Cite

Pleural malignancies, either primary or metastatic, are common and problematic clinical issues in thoracic oncology and pulmonary medicine. Malignant pleural mesothelioma and metastatic pleural effusions often present late in the course of a disease and have a dramatic impact on the patient’s quality of life and survival. Novel approaches to manage mesothelioma and malignant pleural effusions are desperately needed and the pleural space provides a unique platform as an easily accessible body cavity for developing and assessing these treatments and their responses. In this review, we discuss the unique intrapleural chemotherapeutic, immunotherapeutic and genetic treatments that have been investigated, as well as those under current clinical development. While responses have been demonstrated to variable degrees with all these approaches, an integrated multimodality approach incorporating these methods with other anti-neoplastic interventions ultimately will ensure the best responses and patient outcomes.

show abstract

Treatment of mesothelioma with gene-modified PA1STK cells and ganciclovir: a phase I study

Cited by 13 publications

References 17 publications

Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy

Intrapleural immunotherapy: An update on emerging treatment strategies for pleural malignancy

Suicide Gene Therapy against Cancer

Novel Intrapleural Therapies for Malignant Diseases

Contact Info

Product

Resources

About