Trial Watch

Abstract

In 1997, for the first time in history, a monoclonal antibody (mAb), i.e., the chimeric anti-CD20 molecule rituximab, was approved by the US Food and Drug Administration for use in cancer patients. Since then, the panel of mAbs that are approved by international regulatory agencies for the treatment of hematopoietic and solid malignancies has not stopped to expand, nowadays encompassing a stunning amount of 15 distinct molecules. This therapeutic armamentarium includes mAbs that target tumor-associated antigens, as well as molecules that interfere with tumor-stroma interactions or exert direct immunostimulatory effects. These three classes of mAbs exert antineoplastic activity via distinct mechanisms, which may or may not involve immune effectors other than the mAbs themselves. In previous issues of OncoImmunology, we provided a brief scientific background to the use of mAbs, all types confounded, in cancer therapy, and discussed the results of recent clinical trials investigating the safety and efficacy of this approach. Here, we focus on mAbs that primarily target malignant cells or their interactions with stromal components, as opposed to mAbs that mediate antineoplastic effects by activating the immune system. In particular, we discuss relevant clinical findings that have been published during the last 13 months as well as clinical trials that have been launched in the same period to investigate the therapeutic profile of hitherto investigational tumor-targeting mAbs.

Trial Watch: Immunogenic cell death inducers for anticancer chemotherapy

“…40,44,54 Moreover, at least in some cell types, ICD can be provoked by patupilone, an experimental microtubular inhibitor of the epothilone family, [55][56][57] and by 7A7, a monoclonal antibody (mAb) targeting the murine epidermal growth factor receptor (EGFR). 58,59 However, for the reasons mentioned above, FDA-approved epothilones (i.e., ixabepilone, which is licensed for the treatment of breast carcinoma) 60 and EGFR-targeting mAbs (i.e., cetuximab and panitumumab, which are currently employed for the treatment of head and neck cancer and colorectal carcinoma) [61][62][63] may not share this ability with patupilone and 7A7, respectively. Finally, it should be noted that some FDA-approved agents such as digoxin and digitoxin (which are licensed for the treatment of various cardiac disorders), 64 as well as zoledronic acid (which is commonly employed for the treatment of MM or hypercalcemia and bone lesions of oncological origin), 65 are very efficient at boosting the immunogenicity of otherwise non-immunogenic instances of cell death, although they are unable to elicit ICD per se.…”

Beyond the margins: real-time detection of cancer using targeted fluorophores

“…After the approval of the anti-CD20 monoclonal antibody rituximab in 2006, no less than 15 monoclonal antibodies have been approved for cancer therapy 113 . Importantly, once approved, these antibodies can be repurposed for diagnostic applications, such as FGS.…”

New approaches to selectively target cancer-associated matrix metalloproteinase activity

“…Monoclonal antibody approaches have had great successes in cancer treatment [72]. The Her2/Neu targeted monoclonal antibody Herceptin/Trastuzumab has redefined how we treat breast cancer with additional EGF receptor targeted antibodies such as cetuximab and panitumumab also being effective treatments.…”