Electrochemical treatment has been suggested as an effective alternative to local cancer therapy. Nevertheless, its effectiveness decreases when highly aggressive primary tumors are treated. The aim of this research was to understand the growth kinetics of the highly aggressive and metastatic primary F3II tumor growing in male and female BALB/c/Cenp mice under electrochemical treatment. Different amounts of electric charge (6, 9, and 18 C) were used. Two electrodes were inserted into the base, perpendicular to the tumor's long axis, keeping about 1 cm distance between them. Results have shown that the F3II tumor is highly sensitive to direct current. The overall effectiveness (complete response + partial response) of this physical agent was ≥75.0% and observed in 59.3% (16/27) of treated F3II tumors. Complete remission of treated tumors was observed in 22.2% (6/27). An unexpected result was the death of 11 direct current-treated animals (eight females and three males). It is concluded that direct current may be addressed to significantly affect highly aggressive and metastatic primary tumor growth kinetics, including the tumor complete response. Bioelectromagnetics. 39:460-475, 2018. © 2018 Wiley Periodicals, Inc.

Background: The modified Gompertz equation has been proposed to fit experimental data for direct current treated tumors when multiple-straight needle electrodes are individually inserted into the base perpendicular to the tumor long axis. The aim of this work is to evaluate the efficacy of direct current generated by multiple-electrode arrays on F3II mammary carcinoma that grow in the male and female BALB/c/Cenp mice, when multiple-straight needle electrodes and multiple-pairs of electrodes are inserted in the tumor. Methods: A longitudinal and retrospective preclinical study was carried out. Male and female BALB/c/Cenp mice, the modified Gompertz equation, intensities (2, 6 and 10 mA) and exposure times (10 and 20 min) of direct current, and three geometries of multiple-electrodes (one formed by collinear electrodes and two by pair-electrodes) were used. Tumor volume and mice weight were measured. In addition, the mean tumor doubling time, tumor regression percentage, tumor growth delay, direct current overall effectiveness and mice survival were calculated. Results: The greatest growth retardation, mean doubling time, regression percentage and growth delay of the primary F3II mammary carcinoma in male and female mice were observed when the geometry of multiple-pairs of electrodes was arranged in the tumor at 45, 135, 225 and 325 o and the longest exposure time. In addition, highest direct current overall effectiveness (above 66%) was observed for this EChT scheme. Conclusions: It is concluded that electrochemical therapy may be potentially addressed to highly aggressive and metastic primary F3II murine mammary carcinoma and the modified Gompertz equation may be used to fit data of this direct current treated carcinoma. Additionally, electrochemical therapy effectiveness depends on the exposure

The development of prophylactic vaccines at unprecedented speed is necessary to control the global pandemic due to SARS CoV 2 infection. Vaccines approved for use and those under development intend to block viral sites binding to the hosts cellular receptors by means of neutralizing antibodies. Virus infection is mediated by the spike glycoprotein trimer on the virion surface via its receptor binding domain (RBD). Antibody response against this domain is an important outcome of the immunization and correlates well with viral neutralization. Here we show that macromolecular constructs with recombinant RBD conjugated to tetanus toxoid induce a potent immune response in laboratory animals. Some advantages of the immunization with the viral antigen coupled to tetanus toxoid have become evident such as predominantly IgG immune response due to affinity maturation and long term specific B memory cells. This work demonstrates that subunit conjugate vaccines can be an alternative for COVID19 paving the way for other viral conjugate vaccines based on the use of small viral proteins involved in the infection process.

Interaction between epidermal growth factor receptor (EGFR) signaling with GM3 ganglioside expression has been previously described. However, little is known about EGFR and NeuGcGM3 co-expression in cancer patients and their therapeutic implications. In this paper, we evaluate the co-expression of EGFR and NeuGcGM3 ganglioside in tumors from 92 patients and in two spontaneous lung metastasis models of mice (Lewis lung carcinoma (3LL-D122) in C57BL/6 and mammary carcinoma (4T1) in BALB/c). As results, co-expression of EGFR and NeuGcGM3 ganglioside was frequently observed in 63 of 92 patients (68 %), independently of histological subtype. Moreover, EGFR is co-expressed with NeuGcGM3 ganglioside in the metastasis of 3LL-D122 and 4T1 murine models. Such dual expression appears to be therapeutically relevant, since combined therapy with mAbs against these two molecules synergistically increase the survival of mice treated. Overall, our results suggest that NeuGcGM3 and EGFR may coordinately contribute to the tumor cell biology and that therapeutic combinations against these two targets might be a valid strategy to explore.

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.