Combining an EGF-based Cancer Vaccine With Chemotherapy in Advanced Nonsmall Cell Lung Cancer

Abstract

An epidermal growth factor (EGF) vaccine was given before and after standard first line chemotherapy to patients with advanced nonsmall cell lung cancer (NSCLC), to investigate the immunologic and clinical results in a phase 1 study. Twenty patients diagnosed with advanced NSCLC were recruited. Two vaccinations were given before the first line of chemotherapy treatment, with subsequent monthly vaccination after concluding chemotherapy. The EGF vaccination dose was increased compared with previous trials; the primary end points were immunogenicity and safety. Anti-EGF antibody titers were more than 20 times higher than those previously obtained, without any increase in adverse events, serum EGF concentration decreased to undetectable levels in all patients. Ninety-two percent of the evaluated patients (n=13) showed an immunodominant antibody response against the central region on the EGF molecule. High percentages of EGF/EGF receptor binding inhibition were observed, which significantly positively correlated with the increased antibody response against the EGF immunodominant region. Survival of the patients in this study correlates positively with antibody titers. This study has shown that combination of EGF vaccination at high dose, with chemotherapy is feasible and well tolerated higher anti-EGF antibody titers and reduction of serum EGF concentration seen; do not entail an increase in severe adverse events. The correlation of survival with antibody titers observed is being confirmed confirmation in a wider and randomized trial currently ongoing.

Rapid T cell–based identification of human tumor tissue antigens by automated two-dimensional protein fractionation

“…MS was performed in the 5 most immunogenic of a total of 74 2D fractions to identify protein (Supplemental Figure 1; supplemental material available online with this article; doi:10.1172/JCI37646DS1). This MS analysis revealed that immunogenic fractions contained the following well-known TAAs: EGFR (19,20) and Her-2/neu (21,22). To determine whether either of these TAAs was recognized by a population of preexisting memory T cells, we next used well-described synthetic long peptides (EGFR 479-528 , Her-2/neu 351-384 ) (23) as test antigens in ELISPOT assays using blood from the same patient.…”

“…immunogenic epitope in more detail, we synthesized overlapping 20-meric peptides of the respective region ( Figure 6C) and identified S100A9 [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30] as the immunogenic epitope ( Figure 6D). This epitope was recognized both by CD8 + and CD4 + T cells of patient NCH550 ( Figure 6E).…”

Chronic Vaccination with a Therapeutic EGF-Based Cancer Vaccine: A Review of Patients Receiving Long Lasting Treatment

“…This vaccine elicits antibodies against self-EGF and a decrease in plasma EGF concentration [21][22][23][24][25][26][27][28][29]. It has been tested in several clinical trials for the treatment of advanced Non-Small Cell Lung Cancer (NSCLC), in which a significant correlation has been found among anti-EGF antibody titers, decrease in EGF concentration and patient´s survival.…”

HAGE in Triple-Negative Breast Cancer Is a Novel Prognostic, Predictive, and Actionable Biomarker: A Transcriptomic and Protein Expression Analysis

“…Given that the HAGE antigen is immunogenic and is highly associated with TILs, one should consider targeting HAGE along with other CSAs using immunotherapeutic interventions in conjunction with chemotherapy for TNBC. Although in the past, cancer vaccines have had a poor clinical track record due to poor clinical results (34), in recent trials using immunotherapy, clinical outcomes have shown improved progression-free survival, or overall survival (35)(36)(37)(38). In fact, it is proposed that chemotherapies could be used to condition the immune system and tumor, and create an environment in which cancer vaccines have a better chance of success (34,39).…”