Chronic lymphocytic leukemia (CLL) cells genetically modified to express B7-1, ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients

Litzinger, Mary; Foon, Kenneth A.; Sabzevari, Helen; Tsang, Kwong-Yok; Schlom, Jeffrey; Palena, Claudia

doi:10.1007/s00262-008-0611-5

Cited by 17 publications

(9 citation statements)

References 26 publications

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“…Adhesion molecules such as ICAM-1 play a critical role. Our results are in line with previous studies demonstrating the importance of ICAM-1 in the formation of a productive synapse between T cells and either antigen-presenting cells or target cells or between CD19 CAR T cells and malignant B cells from acute lymphoblastic leukemia patients (19)(20)(21)(22).…”

Section: Discussionsupporting

confidence: 93%

CAR T cell entry into tumor islets is a two-step process dependent on IFNγ and ICAM-1

Kantari‐Mimoun

Barrin

Haghiri

et al. 2020

Preprint

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Adoptive transfer of T cells expressing chimeric antigen receptors (CARs) has shown remarkable clinical efficacy against advanced B cell malignancies but not yet against solid tumors. Here, we used fluorescent imaging microscopy and ex vivo assays to compare the early functional responses (migration, Ca2+ and cytotoxicity) of CD20 and EGFR CAR T cells upon contact with malignant B and carcinoma cells. Our results indicate that CD20 CAR T cells rapidly form productive ICAM-1-dependent conjugates with their targets. By comparison, EGFR CAR T cells only interact at first with a subset of carcinoma cells located at the periphery of tumor islets. After this initial peripheral activation, EGFR CAR T cells progressively infiltrate the center of tumor cell regions. The analysis of this two-step entry process shows that activated CAR T cells trigger the upregulation of ICAM-1 on tumor cells in an IFNγ-dependent pathway. The blockade of ICAM-1/LFA-1 interactions prevents CAR T cell recruitment into tumor islets. The requirement for IFNγ and ICAM-1 to enable CAR T cell entry into tumor islets is of significance for improving CAR T strategy in solid tumors.

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Section: Discussionsupporting

confidence: 93%

CAR T cell entry into tumor islets is a two-step process dependent on IFNγ and ICAM-1

Kantari‐Mimoun

Barrin

Haghiri

et al. 2020

Preprint

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“…Because the poxviral vector in PSA-TRICOM expresses multiple costimulatory molecules, infected cells (including tumor cells) can function as APCs [9,30]. Introducing these vectors directly into the prostate may induce a therapeutic pro-inflammatory response caused by ''danger signals.''…”

Section: Discussionmentioning

confidence: 99%

“…Recently, interest in therapeutic vaccines for prostate cancer has increased based on data showing enhanced overall survival in randomized studies [2, 5, 29]. Because the poxviral vector in PSA-TRICOM expresses multiple costimulatory molecules, infected cells (including tumor cells) can function as APCs [9, 30]. Introducing these vectors directly into the prostate may induce a therapeutic pro-inflammatory response caused by “danger signals.” Indeed, in previous studies, patients with advanced cancer have been treated with intratumoral injection of poxviral vectors with good safety profile and indications of clinical activity [12, 13], including a poxviral vector encoding TRICOM molecules in advanced melanoma [11].…”

Section: Discussionmentioning

confidence: 99%

Phase I study of intraprostatic vaccine administration in men with locally recurrent or progressive prostate cancer

Gulley

Heery

Madan

et al. 2013

Cancer Immunol Immunother

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The primary end point of this study was to determine the safety and feasibility of intraprostatic administration of PSA-TRICOM vaccine [encoding transgenes for prostate-specific antigen (PSA) and 3 costimulatory molecules] in patients with locally recurrent or progressive prostate cancer. This trial was a standard 3 + 3 dose escalation with 6 patients each in cohorts 4 and 5 to gather more immunologic data. Nineteen of 21 patients enrolled had locally recurrent prostate cancer after definitive radiation therapy, and 2 had no local therapy. All cohorts received initial subcutaneous vaccination with recombinant vaccinia (rV)-PSA-TRICOM and intraprostatic booster vaccinations with recombinant fowlpox (rF)-PSA-TRICOM. Cohorts 3-5 also received intraprostatic rF-GM-CSF. Cohort 5 received additional subcutaneous boosters with rF-PSA-TRICOM and rF-GM-CSF. Patients had pre- and post-treatment prostate biopsies, and analyses of peripheral and intraprostatic immune cells were performed. There were no dose-limiting toxicities, and the maximum tolerated dose was not reached. The most common grade 2 adverse events were fever (38%) and subcutaneous injection site reactions (33%); the single grade 3 toxicity was transient fever. Overall, 19 of 21 patients on trial had stable (10) or improved (9) PSA values. There was a marked increase in CD4+ (p = 0.0002) and CD8+ (p = 0.0002) tumor infiltrates in post- versus pre-treatment tumor biopsies. Four of 9 patients evaluated had peripheral immune responses to PSA or NGEP. Intraprostatic administration of PSA-TRICOM is safe and feasible and can generate a significant immunologic response. Improved serum PSA kinetics and intense post-vaccination inflammatory infiltrates were seen in the majority of patients. Clinical trials examining clinical end points are warranted.

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“…41–42 It has been shown, moreover, that the T cells generated have higher avidity than peptide-pulsed control dendritic cells or dendritic cells infected with wild-type vector. 43 These findings have led to a clinical trial employing CEA-MUC1-TRICOM (PANVAC) ex vivo infection of human dendritic cells employed as a vaccine in metastatic colorectal cancer patients who have undergone mastectomy, 44–45 as will be discussed below.…”

Section: Ivinnovative Strategies Using Viral-vector Vaccinesmentioning

confidence: 99%

Viral Vector-Based Therapeutic Cancer Vaccines

Larocca¹,

Schlom²

2011

The Cancer Journal

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173

119

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Most viruses are naturally immunogenic and can be engineered to express tumor antigen transgenes. Moreover, many types of recombinant viruses have been shown to infect professional antigen-presenting cells, specifically dendritic cells, and express their transgenes. This enhanced presentation of tumor antigens to the immune system has led to an increase in the frequency and avidity of cytotoxic T-lymphocytes that target tumor cells expressing the tumor antigen(s) encoded in the vaccine vector. Logistically, recombinant viruses can be produced, administered and quality controlled more easily compared to other immunotherapy strategies. The intrinsic properties of each virus have distinct advantages and disadvantages, which can determine their applicability in a particular therapeutic setting. The disadvantage of some vectors is the development of host-induced neutralizing antibodies to the vector itself, thus limiting its continued use. The “off-the-shelf” nature of viral vaccine platforms renders them exceptionally suitable for multicenter randomized trials. This review will describe and discuss the strategies employed and results using viral-based vaccines, with emphasis on phase II and III clinical trials. Future directions will involve the evaluation of viral-based vaccines in the adjuvant and neo-adjuvant settings, in patients with low burden metastatic disease, and in combination with other forms of therapy including immunotherapy.

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Chronic lymphocytic leukemia (CLL) cells genetically modified to express B7-1, ICAM-1, and LFA-3 confer APC capacity to T cells from CLL patients

Cited by 17 publications

References 26 publications

CAR T cell entry into tumor islets is a two-step process dependent on IFNγ and ICAM-1

CAR T cell entry into tumor islets is a two-step process dependent on IFNγ and ICAM-1

Phase I study of intraprostatic vaccine administration in men with locally recurrent or progressive prostate cancer

Viral Vector-Based Therapeutic Cancer Vaccines

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