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

Abstract

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.

Treatment with the thymic polypeptide fraction Biomodulina T potentiates immune responses in older adults and cancer patients: an overview of the most recent studies

“…This is an EGF-depleting immunotherapy that induces neutralizing anti-EGF antibodies that recognize circulating EGF, preventing it from binding to EGFR, and thereby disrupting the signal transduction cascade associated with proliferation and survival signals in tumor cells [44] . The sequential combination treatment of BT and CIMAvax-EGF was found to be safe; as previously reported, neither BT nor CIMAvax-EGF were related to grade 3 or 4 adverse events (AE) and no serious AE were observed [14] . The proposal of sequential combination of BT and CIMAvax-EGF, both after completion of firstline chemotherapy, administered as switch maintenance, benefited a larger percentage of patients than previously described for CIMAvax-EGF alone, met the good antibody response criteria (i.e.…”

“…Terminally differentiated T cells (CD4+EMRA and CD8+EMRA) decreased after BT treatment while CD4+ naïve T cells increased, confirming the ability of BT to expand naïve or early differentiated T cells in the periphery. In addition, CD4+ and CD8+ T cells expressing PD1 were reduced after BT administration, highlighting its likely effects countering "exhaustion" not only in healthy older adults [13] but also in cancer patients [14] .…”

“…Five to seven days after finishing BT administration, patients started treatment with CIMAvax-EGF [14] . This is an EGF-depleting immunotherapy that induces neutralizing anti-EGF antibodies that recognize circulating EGF, preventing it from binding to EGFR, and thereby disrupting the signal transduction cascade associated with proliferation and survival signals in tumor cells [44] .…”

“…In the present paper we review the current and most recent knowledge regarding the effect of Biomodulina T on the immune system in older adults [13] and in patients diagnosed with lung cancer treated with chemotherapy [14] .…”

Changes of peripheral T cell subsets in melanoma patients with immune-related adverse events

“…We have observed a decreased CD4 + to CD8 + T cell ratio in patients with severe irAEs, and in particular an increased frequency of CD8 + EMRA T cells defined as CD8+ CD45RO- CCR7- cells. These T cells were previously associated with various diseases including Alzheimer disease ( 13 ), amyotrophic lateral sclerosis ( 14 ), virus infection ( 15 – 17 ), smoking-associated T cell dysfunction ( 18 ), and cancer ( 9 , 19 ). In HIV infections, CD8 + EMRA T cells were associated with better outcome and control of early viremia ( 16 ).…”