Monoclonal antibodies in drug targeting

Panchagnula, Ramesh; Dey, Chinmoy Sankar

doi:10.1046/j.1365-2710.1997.96475964.x

Cited by 15 publications

(4 citation statements)

References 83 publications

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“…(14,15) Only the 4-7% of tumors that do not have telomerase activity maintain their telomere length by alternate lengthening of telomeres (ALT mechanism). (16) The role of telomerase in the cell immortalization has prompted it to be a potential target for cancer therapy.…”

Section: Discussionmentioning

confidence: 99%

Preparation of Monoclonal Antibodies Against Human Telomerase

2001

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Telomerase, a ribonucleoprotein enzyme that extends telomeres of eukaryotic chromosomes, consists of the catalytic protein submit telomerase reverse transcriptase (TERT) and a telomerase RNA subunit. Nearly 85% of human tumors have tested positive for high telomerase activity. Telomerase activity is very low or not present in normal cells, whereas it is up-regulated in immortalized cells. Telomerase, partially purified from the breast tumor cell line MCF-7, was used to immunize Balb/C mice. Monoclonal antibodies (MAbs) were prepared by conventional hybridoma technology and screened by enzyme-linked immunoadsorbent assay (ELISA), followed by a polymerase chain reaction (PCR) based telomeric amplification repeat protocol (TRAP) assay to detect binding to or inhibition of telomerase activity. Reactive MAbs were found to be of IgM type by mu specific ELISA. Two MAbs were characterized, one that neutralizes telomerase activity in TRAP assay and the other non-neutralizing. In Western blotting, crude telomerase extract and HIV-1 virus lysate (control) were blotted on nitrocellulose membranes and the strips were treated with both MAbs and a nonrelated HIV polymerase-specific MAb, also IgM type. A band of approx. 65-kDa was detected in extracts of 293 cells with both the MAbs, but no reaction occurred with the HIV polymerase-specific MAb used as control. Similarly, when HIV-1 virus lysate strips were treated with HIV polymerase-specific MAb, a 65-kDa band was detected and no band was observed with either of the hybridoma supernatants. These antibodies may be useful for studying regulatory mechanism of telomerase and inhibition of its activity in vitro and in vivo.

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Section: Discussionmentioning

confidence: 99%

Preparation of Monoclonal Antibodies Against Human Telomerase

2001

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“…Antibodies, a biopolymer made of four peptide chains are designed to aid the immune system are nature of molecular recognition machines . Among them monoclonal antibody (mAb), is a unique species of antibody with affinity to only one specific part of an antigen, which can be exploited as sensitive probes to be guided to target cells and organs for drug targeting.…”

Section: Advancements In Methodologies For Drug Deliverymentioning

confidence: 99%

“…Among them monoclonal antibody (mAb), is a unique species of antibody with affinity to only one specific part of an antigen, which can be exploited as sensitive probes to be guided to target cells and organs for drug targeting. By this approach, cytotoxic drugs can be delivered to site‐specific cells like cancer cells with a view to deliver the drugs selectively, to minimize damage to normal cells …”

Section: Advancements In Methodologies For Drug Deliverymentioning

confidence: 99%

Biopolymers and Their Composites for Drug Delivery: A Brief Review

Gopi

Amalraj²,

Sukumaran³

et al. 2018

Macromolecular Symposia

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In recent years, excipient development has become a core area of research in pharmaceutical drug delivery because it influences the formulation development and drug delivery process in various ways. Polymeric drug delivery systems have been of great interest for controlled delivery as they show the great advantage in drug delivery systems because of optimized drug loading and releasing property. Then, the side effects of synthetic polymers far exceed that it leads to some difficulties like they impose dose reduction, treatment delay, or the given therapy is not continuous. With this in mind and together with the need for a protective delivery system for drugs, natural polymeric substances such as biopolymers and their composites are the choice of research as excipient because of their low toxicity, biodegradability, stability, and renewable nature. Furthermore, they have a wide variety of structures, different physiological functions and may provide a variety of biomedical applications, owing to their distinctive properties. The present brief review explores the concept of excipient delivery and the recent advances in both the biopolymers and the methods in the pharmaceutical drug delivery systems.

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“…Several studies showed that targeted delivery of therapeutic agents into cancer cells through monoclonal antibodies (antibody–drug conjugates, ADCs) is considered as a promising strategy to tackle cancer and to increase therapeutic efficacy and reduce toxicity [ 13 , 14 ] because mAbs can recognize the biomarkers of a cancer cell and precisely deliver anticancer drugs into cells as drug carrier [ 15 ]. To date, more than ten ADCs have been approved for clinical applications, and about 80 ADCs are being evaluated in different phases of clinical trials [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions

et al. 2022

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Hematologic malignancies, including leukemia, lymphoma, myeloproliferative disorder and plasma cell neoplasia, are genetically heterogeneous and characterized by an uncontrolled proliferation of their corresponding cell lineages in the bone marrow, peripheral blood, tissues or plasma. Although there are many types of therapeutic drugs (e.g., TKIs, chemotherapy drugs) available for treatment of different malignancies, the relapse, drug resistance and severe side effects due to the lack of selectivity seriously limit their clinical application. Currently, although antibody–drug conjugates have been well established as able to target and deliver highly potent chemotherapy agents into cancer cells for the reduction of damage to healthy cells and have achieved success in leukemia treatment, they still also have shortcomings such as high cost, high immunogenicity and low stability. Aptamers are ssDNA or RNA oligonucleotides that can also precisely deliver therapeutic agents into cancer cells through specifically recognizing the membrane protein on cancer cells, which is similar to the capabilities of monoclonal antibodies. Aptamers exhibit higher binding affinity, lower immunogenicity and higher thermal stability than antibodies. Therefore, in this review we comprehensively describe recent advances in the development of aptamer–drug conjugates (ApDCs) with cytotoxic payload through chemical linkers or direct incorporation, as well as further introduce the latest promising aptamers-based therapeutic strategies such as aptamer–T cell therapy and aptamer–PROTAC, clarifying their bright application, development direction and challenges in the treatment of hematologic malignancies.

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Monoclonal antibodies in drug targeting

Cited by 15 publications

References 83 publications

Preparation of Monoclonal Antibodies Against Human Telomerase

Preparation of Monoclonal Antibodies Against Human Telomerase

Biopolymers and Their Composites for Drug Delivery: A Brief Review

The Landscape of Nucleic-Acid-Based Aptamers for Treatment of Hematologic Malignancies: Challenges and Future Directions

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