Antibody-drug conjugates (ADC) are one of the fastest growing anticancer drugs. This approach comprises a mAb conjugated to the cytotoxic payload via a chemical linker that directed toward a target antigen expressed on the cancer cell surface, reducing systemic exposure and therefore toxicity. ADCs are complex molecules that require careful attention to various components. Selection of an appropriate target, an mAb, cytotoxic payload, and the manner in which the antibody is linked to the payload are key determinants of the safety and efficacy of ADCs. This review provides an overview of the systemic evaluation of each component of an ADC design, improved understanding of the mechanism of action of ADC, and mechanistic pathways involved in ADC resistance and various strategies to optimize ADC design. Moreover, this review also shed light on the current status of ADCs that have gained regulatory approval from the FDA including a description of biology and chemistry, metabolic profiles, adverse events, drug interactions, and the future perspective on combination strategies with other agents, including immunotherapy.
Gene therapy targeting hematopoietic stem cells has been proposed as a potential therapy for numerous genetic disorders affecting hematopoiesis. Moloney murine leukemia retroviral vectors are now widely used for clinical gene transfer into hematopoietic progenitors and progeny. However, maintaining expression of therapeutic genes inserted via moloney murine leukemia virus (MoMLV)-based vectors has proven to be more difficult than previously expected. In this study, an MND-IL-2R vector containing IL-2Rc gamma cDNA to treat X-linked severe combined immunodeficiency (X-SCID) was constructed from an MND vector that was modified by substituting the myeloproliferative sarcoma virus (MPSV) enhancer for that of MoMLV, deleting the negative control region located in the long terminal repeat (LTR) as an enhancer, and replacing the primer binding site (PBS) of MoMLV with the PBS of the endogenous murine retrovirus dl587rev. This vector was transduced into human CD34 + progenitor cells with comparable efficiency to that of the MoMLV-based vector. The use of this newly created vector may be advantageous for gene therapy of X-SCID.
Objective EAF2 plays an important role in transcription elongation and the regulation of gene expression in mammalian cells. EAF2’s depletion has been demonstrated to enhance cell proliferation and greatly increase the risk of cancer. Even so, its expression and prognostic role in cervical cancer (CC) remains controversial. Methods To solve this issue, we comprehensively investigated the role of EAF2 in CC through various databases including ONCOMINE, UALCAN, Kaplan-Meier Plotter and TIMER. Results In all, we found that the EAF2 was highly expressed in CC tissue and was significantly correlated with better patient survival. Among the CNAs, amplification was the dominant alteration. Then the co-expression profile and enrichment analysis of EAF2 were related to the potential signaling pathways. The function of genes such as Kinase LYN, mi-RNA133A-133B and transcription factor OCT1 were also enriched in CC. The positively relation EAF2 expression to 6 immune cells revealed that EAF2 expression may affect development of patients with CC partially due to immune infiltration. Conclusions Taken together, our data suggest that EAF2 might be a potential prognostic marker and therapeutic target for CC patients.
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