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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Study protocol

Phase I study of an active immunotherapy for asymptomatic phase Lymphoplasmacytic lymphoma with DNA vaccines encoding antigen-chemokine fusion: study protocol

Authors: Sheeba K. Thomas, Soung-chul Cha, D. Lynne Smith, Kun Hwa Kim, Sapna R. Parshottam, Sheetal Rao, Michael Popescu, Vincent Y. Lee, Sattva S. Neelapu, Larry W. Kwak

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

There is now a renewed interest in cancer vaccines. Patients responding to immune checkpoint blockade usually bear tumors that are heavily infiltrated by T cells and express a high load of neoantigens, indicating that the immune system is involved in the therapeutic effect of these agents; this finding strongly supports the use of cancer vaccine strategies. Lymphoplasmacytic lymphoma (LPL) is a low grade, incurable disease featuring an abnormal proliferation of Immunoglobulin (Ig)-producing malignant cells. Asymptomatic patients are currently managed by a “watchful waiting” approach, as available therapies provide no survival advantage if started before symptoms develop. Idiotypic determinants of a lymphoma surface Ig, formed by the interaction of the variable regions of heavy and light chains, can be used as a tumor-specific marker and effective vaccination using idiotypes was demonstrated in a positive controlled phase III trial.

Methods

These variable region genes can be cloned and used as a DNA vaccine, a delivery system holding tremendous potential for streamlining vaccine production. To increase vaccination potency, we are targeting antigen-presenting cells (APCs) by fusing the antigen with a sequence encoding a chemokine (MIP-3α), which binds an endocytic surface receptor on APCs. Asymptomatic phase LPL is an excellent model to test our vaccine since patients have not received chemotherapeutics that interfere with innate immune function and have low tumor burden. We are evaluating the safety of this next-generation DNA vaccine in a first-in-human clinical trial currently enrolling asymptomatic LPL patients. To elucidate the mode of action of this vaccine, we will assess its ability to generate tumor-specific immune responses and examine changes in the immune profile of both the peripheral blood and bone marrow.

Discussion

This vaccine could shift the current paradigm of clinical management for patients with asymptomatic LPL and inform development of other personalized approaches.

Trial registration

ClinicalTrials.​gov identifier NCT01209871; registered on September 24, 2010.
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Metadata
Title
Phase I study of an active immunotherapy for asymptomatic phase Lymphoplasmacytic lymphoma with DNA vaccines encoding antigen-chemokine fusion: study protocol
Authors
Sheeba K. Thomas
Soung-chul Cha
D. Lynne Smith
Kun Hwa Kim
Sapna R. Parshottam
Sheetal Rao
Michael Popescu
Vincent Y. Lee
Sattva S. Neelapu
Larry W. Kwak
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4094-2

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