Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule

Popa, Xitllaly; García, Beatriz; Fuentes, Karla; Huerta, Vivian; Álvarez, Karen Valdés; Viada, Carmen; Neninger, Elia; Rodríguez, Pedro C.; González, Zuyén; González, Amnely; Crombet, Tania; Mazorra, Zaima

doi:10.1080/2162402x.2020.1762465

Cited by 10 publications

(8 citation statements)

References 47 publications

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“…CIMAvax-EGF has proven to be safe, even after extended use, and capable to keep EGF serum concentration below detectable levels ( 23 , 24 ). The anti-EGF antibody response did not cross-react with other EGFR ligands, such as TGF alpha and amphiregulin ( 22 , 25 ). Notably, in some patients, TGF alpha augmented after 6 months of CIMAvax-EGF, while amphiregulin concentration did not change overtime ( 25 ).…”

Section: Cimavax-egf Immunotherapymentioning

confidence: 97%

“…The anti-EGF antibody response did not cross-react with other EGFR ligands, such as TGF alpha and amphiregulin ( 22 , 25 ). Notably, in some patients, TGF alpha augmented after 6 months of CIMAvax-EGF, while amphiregulin concentration did not change overtime ( 25 ). The increase of one or more ligands after effective EGFR blockade has been reported before ( 26 , 27 ).…”

Section: Cimavax-egf Immunotherapymentioning

confidence: 97%

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The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer

Ramos

Santos-Morales

et al. 2021

Front. Oncol.

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Advanced non-small cell lung cancer (NSCLC) has faced a therapeutic revolution with the advent of tyrosine kinase inhibitors (TKIs) and immune checkpoints inhibitors (ICIs) approved for first and subsequent therapies. CIMAvax-EGF is a chemical conjugate between human-recombinant EGF and P64, a recombinant protein from Neisseria meningitides, which induces neutralizing antibodies against EGF. In the last 15 years, it has been extensively evaluated in advanced NSCLC patients. CIMAvax-EGF is safe, even after extended use, and able to keep EGF serum concentration below detectable levels. In a randomized phase III study, CIMAvax-EGF increased median overall survival of advanced NSCLC patients with at least stable disease after front-line chemotherapy. Patients bearing squamous-cell or adenocarcinomas and serum EGF concentration above 870 pg/ml had better survival compared to control patients treated with best supportive care as maintenance, confirming tumors’ sensitivity to the EGF depletion. This manuscript reviews the state-of-the-art NSCLC therapy and proposes the most promising scenarios for evaluating CIMAvax-EGF, particularly in combination with TKIs or ICIs. We hypothesize that the optimal combination of CIMAvax-EGF with established therapies can further contribute to transform advanced cancer into a manageable chronic disease, compatible with years of good quality of life.

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Section: Cimavax-egf Immunotherapymentioning

confidence: 97%

Section: Cimavax-egf Immunotherapymentioning

confidence: 97%

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer

Ramos

Santos-Morales

et al. 2021

Front. Oncol.

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“…However, a significant OS benefit was observed in a post hoc analysis using Harrington–Fleming test (a weighted log-rank test) in the safety population and was also exhibited among the subgroup of patients who received at least four vaccine doses [28] . An exploratory analysis suggested that the quantity and quality of anti-EGF antibodies were potential biomarkers to predict the efficacy of the CIMAvax-EGF vaccine [29] . No comparison was made between using the CIMAvax-EGF vaccine as a switch maintenance treatment and as a standard maintenance therapy, which made this study less convincing.…”

Section: Promising Strategies Of Immunotherapy In Advanced or Metasta...mentioning

confidence: 99%

Current immune therapeutic strategies in advanced or metastatic non-small-cell lung cancer

Liu

et al. 2023

Chinese Medical Journal

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Immune escape mechanisms in non-small cell lung cancer (NSCLC) can disrupt every step of the anti-cancer immune response. In recent years, an increased understanding of the specific mechanisms fueling immune escape has allowed for the development of numerous immunotherapeutic treatments that have been introduced into the clinical practice. The advent of immunotherapy has dramatically changed the current treatment landscape of advanced or metastatic NSCLC because of its durable efficacy and manageable toxicity. In this review, we will first present a brief overview of recent evidence on immune escape mechanisms in NSCLC. We will then discuss the current promising immunotherapeutic strategies in advanced or metastatic NSCLC tumors.

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“…Unbound labeled antibody is subsequently removed from all wells by washing, and the solution of diethanolamine with substrate para-nitrophenylphosphate is applied to the plate. The enzyme/substrate reaction provokes a yellow color development and absorbance is measured at 405 nm in an ELISA plate reader after stopping of the reaction (13,18).…”

Section: Measurements Of Anti-egf Antibody Titers and Egf Concentrationsmentioning

confidence: 99%

Thymic Polypeptide Fraction Biomodulina T Decreases Exhausted and Terminally Differentiated EMRA T Cells in Advanced Lung Cancer Patients Treated With Platinum-Based Chemotherapy

Suárez

Catala²,

Peña³

et al. 2022

Front. Oncol.

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Lung cancer is the second cause of cancer related deaths worldwide. Chemotherapy and immunotherapy represent the current standard of care for advanced NSCLC. Platinum-based chemotherapy expands late-differentiated T cell populations. Therefore, immune restoration after chemotherapy to adjuvate the immunotherapeutic potential could be crucial. The aim of this study was to evaluate the effect of Biomodulina T (BT), a thymic polypeptide fraction, on peripheral lymphocytes subpopulations in the context of cancer disease. Additionally, whether these effects might induce a better response to CIMAvax-EGF, an epidermal growth factor (EGF) depleting immunotherapy. Eighteen advanced NSCLC patients were evaluated after being treated with platinum-based chemotherapy. We found that the frequency of terminally differentiated effector T cells re-expressing CD45RA (EMRA) CD4+ (p=0.0031) and CD8+ (p=0.0372) T cells decreased with the administration of BT, whereas CD4+ naive T cells increase in more than 70% of the patients. Remarkably, CD4+ and CD8+ T lymphocytes expressing programmed cell death receptor-1 (PD1) significantly decreased after BT administration (p=0.0005 and p<0.0001, respectively). We also found an enhancement of the anti-EGF antibody response with a large percentage of patients treated with CIMAvax-EGF reaching the good antibody response condition after four vaccine doses. Moreover, the median overall survival of patients treated with CIMAvax-EGF was 16.09 months. In conclusion, our results suggest that the immunorestoration generated by the administration of BT after first-line chemotherapy may induce a better immune response to CIMAvax-EGF that could translate into the clinical benefit of patients diagnosed with advanced NSCLC.

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Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule

Abstract: Mazorra (2020) Anti-EGF antibodies as surrogate biomarkers of clinical efficacy in stage IIIB/IV non-small-cell lung cancer patients treated with an optimized CIMAvax-EGF vaccination schedule, OncoImmunology, 9:1, 1762465,

Cited by 10 publications

References 47 publications

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer

The Position of EGF Deprivation in the Management of Advanced Non-Small Cell Lung Cancer

Current immune therapeutic strategies in advanced or metastatic non-small-cell lung cancer

Thymic Polypeptide Fraction Biomodulina T Decreases Exhausted and Terminally Differentiated EMRA T Cells in Advanced Lung Cancer Patients Treated With Platinum-Based Chemotherapy

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