Immunotherapy in skin cancers - A narrative review

Immunotherapy, in the context of cancers, involves the use of various drugs to stimulate the immune system to target cancer cells. Immunotherapy is being increasingly used for cutaneous malignancies, especially melanoma. Immunity plays an important part in protection against cancer. One of the factors limiting the effectiveness of host immunity is improper recognition of cancer cells. Sometimes, despite recognizing the cancer cells as abnormal, the immune response, for various reasons might not be strong enough to deal effectively with the cancer cells. Immunotherapy basically tries to address the two points mentioned above by improving the capacity of the immune system to recognize and effectively destroy cancer cells. In skin cancers, immunotherapy is best established for melanomas, but is increasingly being used for non-melanoma skin cancers too. This article reviews some of the general concepts about immunotherapy in cancer and discusses in detail, the available options and future possibilities in the applications of immunotherapy in skin cancer.

High-Effective Gene Delivery Based on Cyclodextrins Multivalent Assembly in Target Cancer Cells

Nucleic acids condensation and controlled release remain significant challenges of gene therapy in chemical biology and nanotechnology fields. In this work, we have reported a polysaccharide supramolecular assembly constructed by...

Metal-Based Nanomaterials Incorporate with Ultrasound as Acceptable Approach towards Cancer Therapy

Among current biological researches, there have a plenty of works related cancer therapy issues by using functional or pure-phased composites in non-invasive strategies. Especially in fabricating anticancer candidates, functional composites are divided into different sorts with different characteristics. Additionally, nanotechnology provides various approaches in utilizing composites’ functionality for cancer diagnostics and therapeutics. Compared with previous Photodynamic Therapy (PDT), Photo-Thermal Therapy (PTT), chemotherapy and radiotherapy, ultrasound is used to activate sonosensitizer to produce cytotoxic Reactive Oxygen Species (ROS) toward target cancer cells. In recent years, the form of Sonodynamic Therapy (SDT) has been making much effort to develop highly efficient metal based Nanomaterials (NMs) as sonosensitizers, which can efficiently generate ROS and has the advantages of deeper tissue penetration. However, the traditional sonosensitizers, such as porphyrins, hypericin, and curcumins suffer from complex synthesis, poor water solubility, and low tumor targeting efficacy. For contrasting this limitation, the metal based inorganic NMs show biocompatibility, controllable physicochemical properties, and ease of achieving multifunctional properties, which greatly expanded their application in SDT. In this review, we systematically summarize the metal based inorganic NMs as carrier of molecular sonosensitizers, and produce ROS under ultrasound. Moreover, the prospects of advanced metal based further materials application are also discussed.

Recent advances and challenges of bispecific antibodies in solid tumors

Cancer immunotherapy has made remarkable progress in the past decade. Bispecific antibodies (BsAbs) have acquired much attention as the next generation strategy of antibody-target cancer immunotherapy, which overwhelmingly focus on T cell recruitment and dual receptors blockade. So far, BsAb drugs have been proved clinically effective and approved for the treatment of hematologic malignancies, but no BsAb have been approved in solid tumors. Numerous designed BsAb drugs for solid tumors are now undergoing evaluation in clinical trials. In this review, we will introduce the formats of bispecific antibodies, and then update the latest preclinical studies and clinical trials in solid tumors of BsAbs targeting EpCAM, CEA, PMSA, ErbB family, and so on. Finally, we discuss the BsAb-related adverse effects and the alternative strategy for future study.

Protein Tyrosine Phosphatases: Mechanisms in Cancer

Protein tyrosine kinases, especially receptor tyrosine kinases, have dominated the cancer therapeutics sphere as proteins that can be inhibited to selectively target cancer. However, protein tyrosine phosphatases (PTPs) are also an emerging target. Though historically known as negative regulators of the oncogenic tyrosine kinases, PTPs are now known to be both tumor-suppressive and oncogenic. This review will highlight key protein tyrosine phosphatases that have been thoroughly investigated in various cancers. Furthermore, the different mechanisms underlying pro-cancerous and anti-cancerous PTPs will also be explored.

Copper-64-Labeled 1C1m-Fc, a New Tool for TEM-1 PET Imaging and Prediction of Lutetium-177-Labeled 1C1m-Fc Therapy Efficacy and Safety

1C1m-Fc, a promising anti-TEM-1 DOTA conjugate, was labeled with 64Cu to target cancer cells for PET imaging and predicting the efficacy and safety of a previously studied [177Lu]Lu-1C1m-Fc companion therapy. DOTA-conjugated 1C1m-Fc was characterized by mass spectrometry, thin layer chromatography and immunoreactivity assessment. PET/CT and biodistribution studies were performed in human neuroblastoma xenografted mice. Absorbed doses were assessed from biodistribution results and extrapolated to 177Lu based on the [64Cu]Cu-1C1m-Fc data. The immunoreactivity was ≥ 70% after 48 h of incubation in serum, and the specificity of [64Cu]Cu-1C1m-Fc for the target was validated. High-resolution PET/CT images were obtained, with the best tumor-to-organ ratios reached at 24 or 48 h and correlated with results of the biodistribution study. Healthy organs receiving the highest doses were the liver, the kidneys and the uterus. [64Cu]Cu-1C1m-Fc could be of interest to give an indication of 177Lu dosimetry for parenchymal organs. In the uterus and the tumor, characterized by specific TEM-1 expression, the 177Lu-extrapolated absorbed doses are overestimated because of the lack of later measurement time points. Nevertheless, 1C1m-Fc radiolabeled with 64Cu for imaging would appear as an interesting radionuclide companion for therapeutic application with [177Lu]Lu-1C1m-Fc.

Antibody-Based Immunotoxins for Colorectal Cancer Therapy

Monoclonal antibodies (mAbs) are included among the treatment options for advanced colorectal cancer (CRC). However, while these mAbs effectively target cancer cells, they may have limited clinical activity. A strategy to improve their therapeutic potential is arming them with a toxic payload. Immunotoxins (ITX) combining the cell-killing ability of a toxin with the specificity of a mAb constitute a promising strategy for CRC therapy. However, several important challenges in optimizing ITX remain, including suboptimal pharmacokinetics and especially the immunogenicity of the toxin moiety. Nonetheless, ongoing research is working to solve these limitations and expand CRC patients’ therapeutic armory. In this review, we provide a comprehensive overview of targets and toxins employed in the design of ITX for CRC and highlight a wide selection of ITX tested in CRC patients as well as preclinical candidates.

The Role of Exosomes and Their Applications in Cancer

Exosomes are very small extracellular vesicles secreted by multiple cell types and are extensively distributed in various biological fluids. Recent research indicated that exosomes can participate in regulating the tumor microenvironment and impacting tumor proliferation and progression. Due to the extensive enrollment in cancer development, exosomes have become a focus of the search for a new therapeutic method for cancer. Exosomes can be utilized for the therapeutic delivery of small molecules, proteins and RNAs to target cancer cells with a high efficiency. Exosome-carried proteins, lipids and nucleic acids are being tested as promising biomarkers for cancer diagnosis and prognosis, even as potential treatment targets for cancer. Moreover, different sources of exosomes exhibit multiple performances in cancer applications. In this review, we elaborate on the specific mechanism by which exosomes affect the communication between tumors and the microenvironment and state the therapeutic and diagnostic applications of exosomes in cancers.

Functionalized Poly(N-isopropylacrylamide)-Based Microgels in Tumor Targeting and Drug Delivery

Over the past several decades, the development of engineered small particles as targeted and drug delivery systems (TDDS) has received great attention thanks to the possibility to overcome the limitations of classical cancer chemotherapy, including targeting incapability, nonspecific action and, consequently, systemic toxicity. Thus, this research aims at using a novel design of Poly(N-isopropylacrylamide) p(NIPAM)-based microgels to specifically target cancer cells and avoid the healthy ones, which is expected to decrease or eliminate the side effects of chemotherapeutic drugs. Smart NIPAM-based microgels were functionalized with acrylic acid and coupled to folic acid (FA), targeting the folate receptors overexpressed by cancer cells and to the chemotherapeutic drug doxorubicin (Dox). The successful conjugation of FA and Dox was demonstrated by dynamic light scattering (DLS), Fourier-transform infrared (FTIR) spectroscopy, thermogravimetric analysis (TGA), UV-VIS analysis, and differential scanning calorimetry (DSC). Furthermore, viability assay performed on cancer and healthy breast cells, suggested the microgels’ biocompatibility and the cytotoxic effect of the conjugated drug. On the other hand, the specific tumor targeting of synthetized microgels was demonstrated by a co-cultured (healthy and cancer cells) assay monitored using confocal microscopy and flow cytometry. Results suggest successful targeting of cancer cells and drug release. These data support the use of pNIPAM-based microgels as good candidates as TDDS.