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Microsphere-Delivered Cytokines in Increasing Tumor Response in Lymphocytes From Patients With Head and Neck Cancer

2014-08-27 03:22:14 | BioPortfolio

Summary

RATIONALE: Studying samples of tumor tissue from patients with cancer in the laboratory may help doctors learn more about how interleukin-2, interleukin-12, and GM-CSF delivered in microspheres increase the body's ability to kill tumor cells.

PURPOSE: This laboratory study is looking at microsphere-delivered cytokines to see if they increase tumor response in lymphocytes from patients with head and neck cancer.

Description

OBJECTIVES:

- Determine whether local sustained delivery of cytokines (interleukin-2, interleukin-12, or sargramostim [GM-CSF]) in biodegradable microspheres augments antitumor response in human peripheral blood lymphocytes (PBLs) obtained from patients with squamous cell carcinoma of the head and neck, as evaluated in a human/SCID chimeric mouse model.

- Assess the potential of cytokine-loaded microspheres combined with dendritic cells (pulsed with tumor peptide) obtained from these patients to enhance long-term immunity against the tumor, as evaluated in a human/SCID chimeric mouse model.

- Evaluate the antitumor effect of the more effective approach (objective I or II) against established tumors in the mouse model.

OUTLINE: Biopsies of tumor are obtained during surgical resection. Patients undergo phlebotomy or leukapheresis to obtain peripheral blood lymphocytes (PBLs). PBLs, tumor tissue, and cytokine-loaded microspheres are coengrafted into SCID mice. Tumor growth and immune response are determined.

Dendritic cells are obtained from PBLs, expanded in culture, and pulsed with either autologous tumor cell lysates or peptide eluted from the tumor cells. The dendritic cells are coengrafted with tumor cells, PBLs, and cytokine-loaded microspheres into SCID mice. The mice are then challenged with autologous tumor cells, and antitumor response is determined.

PROJECTED ACCRUAL: A total of 50 patients will be accrued for this study.

Study Design

N/A

Conditions

Head and Neck Cancer

Intervention

aldesleukin, recombinant interleukin-12, sargramostim, immunologic technique, biopsy

Status

Completed

Source

National Cancer Institute (NCI)

Results (where available)

View Results

Links

Published on BioPortfolio: 2014-08-27T03:22:14-0400

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Medical and Biotech [MESH] Definitions

An interleukin receptor subunit that was originally discovered as a component of the INTERLEUKIN 2 RECEPTOR. It was subsequently found to be a component of several other receptors including the INTERLEUKIN 4 RECEPTOR, the INTERLEUKIN 7 RECEPTOR, the INTERLEUKIN-9 RECEPTOR, the INTERLEUKIN-15 RECEPTOR, and the INTERLEUKIN-21 RECEPTOR. Mutations in the gene for the interleukin common gamma chain have been associated with X-LINKED COMBINED IMMUNODEFICIENCY DISEASES.

Cell surface receptors for INTERLEUKIN-13. Included under this heading are the INTERLEUKIN-13 RECEPTOR ALPHA2 which is a monomeric receptor and the INTERLEUKIN-4 RECEPTOR TYPE II which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13.

A cytokine subunit that is a component of both interleukin-12 and interleukin-23. It binds to the INTERLEUKIN-12 SUBUNIT P35 via a disulfide bond to form interleukin-12 and to INTERLEUKIN-23 SUBUNIT P19 to form interleukin-23.

An interleukin receptor subunit with specificity for INTERLEUKIN-13. It dimerizes with the INTERLEUKIN-4 RECEPTOR ALPHA SUBUNIT to form the TYPE II INTERLEUKIN-4 RECEPTOR which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13. Signaling of this receptor subunit occurs through the interaction of its cytoplasmic domain with JANUS KINASES such as the TYK2 KINASE.

An interleukin receptor subtype found on both hematopoietic and non-hematopoietic cells. It is a membrane-bound heterodimer that contains the INTERLEUKIN-4 RECEPTOR ALPHA SUBUNIT and the INTERLEUKIN-13 RECEPTOR ALPHA1 SUBUNIT. Although commonly referred to as the interleukin-4 type-II receptor this receptor has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13

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