CD4⁺ T cell‐mediated HER‐2/neu‐specific tumor rejection in the absence of B cells

Abstract

HER-2/neu (HER-2

CD4-Positive T Lymphocytes Provide a Neuroimmunological Link in the Control of Adult Hippocampal Neurogenesis

“…B cell-deficient ( MT) mice were generated and bred in the animal facility of the Max Delbrück Center, as described elsewhere (27). The animal study was approved by Landesamt für Gesundheit und Technische Sicherheit Berlin.…”

“…Armenian hamster IgG was used as control (R&D Systems), depletion lasting over 7 days (27). Specific depletion was confirmed using the FITC-RM-4-4 (anti-CD4; BD Pharmingen) and PE-53-5.6.7 (anti-CD8; BD Pharmingen) to analyze PBL after T cell depletion.…”

Humoral Epitope-Spreading Following Immunization with a HER-2/neu Peptide Based Vaccine in Cancer Patients

“…A neu-specific cellular response has been shown to mediate an antitumor effect after active immunization in neutransgenic mice and there is some evidence that B cells may not be the most important immune effectors in the therapeutic response (6). However, other evidence demonstrates that both antibody and T cell immunity are required to elicit an antitumor effect in neu-transgenic mice (7,8).…”

CCL19 as an adjuvant for intradermal gene gun immunization in a Her2/neu mouse tumor model: improved vaccine efficacy and a role for B cells as APC

“…The latter point is indeed supported by a strong antiHer2/neu antibody response after gene gun immunization (but not after i.m. vaccination) and by depletion experiments in the same tumor model as well as in B16 melanoma showing that CD4 þ T cells play a pivotal role for tumor protection 27,42,43 Furthermore, it has previously been demonstrated in a Her2/neu þ tumor model, that multiple antigen-specific and non-specific immune mechanisms are responsible for tumor rejection, 44 (2) splenic T cells (which were used in our assays) do not sufficiently reflect systemic responses or responses at the tumor site and (3) T-cell assays used did not include the most relevant tumor rejection epitopes. Although our data show that Her2/neu vaccines are still immunogenic in B-cell-deficient mice, they also show that B cells are involved at least in mediating the adjuvant activity of CCL19.…”

“…The preclinical Her2/neu mouse tumor model used in the current study is well established and has previously been applied in other investigations. [27][28][29] It is particularly appropriate for the initial evaluation of adjuvants for genetic immunization and successful candidate molecules may subsequently be evaluated in transgenic mouse models, which are more suitable with regard to the preexisting tolerance towards tumor antigens observed in patients. 30 Intramuscular application of pDNA(Her2/neu) alone was not able to induce protection from a subsequent tumor challenge, whereas intradermal delivery of the same vaccine by gene gun led to longterm protection in 40% of the animals.…”