Find results with:

Add another field

Search by date

to

Searching collections:

Dartmouth Dissertations

Add or remove collections

Home Dartmouth Dissertations Page 1

Reference URL

To link to the entire object, paste this link in email, IM or document

To embed the entire object, paste this HTML in website

To link to this page, paste this link in email, IM or document

To embed this page, paste this HTML in website

Endogenous leukocyte activation by chimeric antigen receptor T cell immunotherapy / by Paul Spear.

you wish to report:

Your comment:

Your Name:

Submit

Cancel

...

Back to top

Powered by CONTENTdm®

Author	Spear, Paul.
Title	Endogenous leukocyte activation by chimeric antigen receptor T cell immunotherapy / by Paul Spear.
Date	2013
Abstract	Many protocols for adoptive T cell therapy (ACT) include preparative conditioning strategies to deplete host lymphocytes prior to T cell infusion. Total body irradiation and high-dose chemotherapy regimens not only relieve immunosuppression, but increase persistence of the transferred T cells in the host. These preconditioning regimens appear to correlate with improved clinical responses following adoptive T cell therapy. However, they can also result in the death of healthy cells and reduce the quality of life for patients. In addition, some clinical trials employing host conditioning strategies in combination with adoptive T cell transfer have demonstrated tumor persistence and relapse as a result of the outgrowth of antigenic variants. Harnessing endogenous lymphocytes is one method to broaden the tumor-specific T cell repertoire and eliminate tumor cells that have lost the targeted antigen following adoptive T cell therapy. Recent evidence suggests that transferred T cells may eradicate tumors without the need for prior conditioning, indicating that T cell therapies can enhance tumor elimination by relieving immunosuppression and promoting endogenous immunity. Collectively, the data presented in this thesis challenge the popular paradigm that lymphodepleting regimens are crucial for optimal efficacy of all ACTs. NKG2D chimeric antigen receptor (CAR) T cell therapy mounted robust anti-tumor immunity in unconditioned (immune intact) hosts, and this therapy harnessed endogenous macrophage and T cell anti-tumor immunity for superior elimination of ovarian tumors. Moreover, these data suggest that endogenous immunity broadens the specificity of the anti-tumor immune response and is critical for the control of antigenic tumor variants. The data also elucidate unique effector mechanisms employed by the transfused CD8⁺ and CD4⁺ T cells in awakening endogenous macrophage and T cell immunity. These findings advance the T cell therapy field by improving the understanding of the mechanisms that are required
Description	xv, 206 leaves : ill. 28 cm.
Format	application/pdf
Advisor	Charles L. Sentman, Paul Guyre, Mary Jo Turk, Nejat K. Egilmez
College	Dartmouth Medical School. Department of Microbiology and Immunology.
Issuing Body	Dartmouth Dissertations are made available through the Dartmouth Digital Library.
Degree	Thesis (Ph.D.)--Dartmouth College.
Copyright	All rights reserved. No part of this book may be reproduced in any form by any electronic or mechanical means without permission in writing from the author.
DOI	http://dx.doi.org/10.1349/ddlp.1006

Find results with:

Searching collections:

Home Dartmouth Dissertations Page 1

Endogenous leukocyte activation by chimeric antigen receptor T cell immunotherapy / by Paul Spear.

Object Description

Description

Endogenous leukocyte activation by chimeric antigen...

Endogenous leukocyte activation by chimeric antigen...

	All
	Pages Enter page numbers or page ranges separated by commas. For example: 1,3,5-12