PMID- 28990505
OWN - NLM
STAT- MEDLINE
DCOM- 20190624
LR  - 20190624
IS  - 1875-533X (Electronic)
IS  - 0929-8673 (Linking)
VI  - 26
IP  - 6
DP  - 2019
TI  - Biological Therapy of Hematologic Malignancies: Toward a Chemotherapy- free Era.
PG  - 1002-1018
LID - 10.2174/0929867324666171006144725 [doi]
AB  - Less than 70 years ago, the vast majority of hematologic malignancies were 
      untreatable diseases with fatal prognoses. The development of modern chemotherapy 
      agents, which had begun after the Second World War, was markedly accelerated by 
      the discovery of the structure of DNA and its role in cancer biology and tumor 
      cell division. The path travelled from the first temporary remissions observed in 
      children with acute lymphoblastic leukemia treated with single-agent 
      antimetabolites until the first cures achieved by multi-agent chemotherapy 
      regimens was incredibly short. Despite great successes, however, conventional 
      genotoxic cytostatics suffered from an inherently narrow therapeutic index and 
      extensive toxicity, which in many instances limited their clinical utilization. 
      In the last decade of the 20th century, increasing knowledge on the biology of 
      certain malignancies resulted in the conception and development of first 
      molecularly targeted agents designed to inhibit specific druggable molecules 
      involved in the survival of cancer cells. Advances in technology and genetic 
      engineering enabled the production of structurally complex anticancer 
      macromolecules called biologicals, including therapeutic monoclonal antibodies, 
      antibody-drug conjugates and antibody fragments. The development of drug delivery 
      systems (DDSs), in which conventional drugs were attached to various types of 
      carriers including nanoparticles, liposomes or biodegradable polymers, 
      represented an alternative approach to the development of new anticancer agents. 
      Despite the fact that the antitumor activity of drugs attached to DDSs was not 
      fundamentally different, the improved pharmacokinetic profiles, decreased toxic 
      side effects and significantly increased therapeutic indexes resulted in their 
      enhanced antitumor efficacy compared to conventional (unbound) drugs. Approval of 
      the first immune checkpoint inhibitor for the treatment of cancer in 2011 
      initiated the era of cancer immunotherapy. Checkpoint inhibitors, bispecific 
      T-cell engagers, adoptive T-cell approaches and cancer vaccines have joined the 
      platform so far, represented mainly by recombinant cytokines, therapeutic 
      monoclonal antibodies and immunomodulatory agents. In specific clinical 
      indications, conventional drugs have already been supplanted by multi-agent, 
      chemotherapy-free regimens comprising diverse immunotherapy and/or targeted 
      agents. The very distinct mechanisms of the anticancer activity of new 
      immunotherapy approaches not only call for novel response criteria, but might 
      also change fundamental treatment paradigms of certain types of hematologic 
      malignancies in the near future.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Klener, Pavel Jr
AU  - Klener P Jr
AD  - First Medical Department- Dept. of Hematology, First Faculty of Medicine and 
      General University Hospital, Charles University, Czech Republic.
AD  - Institute of Pathological Physiology, First Faculty of Medicine, Charles 
      University, Czech Republic.
FAU - Etrych, Tomas
AU  - Etrych T
AD  - Department of biomedical polymers, Institute of Macromolecular Chemistry of the 
      Czech Academy of Sciences, Heyrovskeho namesti 2, 162 06 Prague, Czech Republic.
FAU - Klener, Pavel
AU  - Klener P
AD  - First Medical Department- Dept. of Hematology, First Faculty of Medicine and 
      General University Hospital, Charles University, Czech Republic.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Med Chem
JT  - Current medicinal chemistry
JID - 9440157
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Cancer Vaccines)
SB  - IM
MH  - Antibodies, Monoclonal/therapeutic use
MH  - Cancer Vaccines/immunology
MH  - Hematologic Neoplasms/*therapy
MH  - Humans
MH  - Immunotherapy/methods
OTO - NOTNLM
OT  - Hematologic malignancies
OT  - antibody- drug conjugates (ADC)
OT  - biodegradable polymers
OT  - biologicals
OT  - bispecific T-cell engagers (BiTE)
OT  - immune checkpoint inhibitors
OT  - immunomodulatory agents (IMiD)
OT  - monoclonal antibodies.
EDAT- 2017/10/11 06:00
MHDA- 2019/06/25 06:00
CRDT- 2017/10/10 06:00
PHST- 2017/02/28 00:00 [received]
PHST- 2017/09/07 00:00 [revised]
PHST- 2017/09/15 00:00 [accepted]
PHST- 2017/10/11 06:00 [pubmed]
PHST- 2019/06/25 06:00 [medline]
PHST- 2017/10/10 06:00 [entrez]
AID - CMC-EPUB-86243 [pii]
AID - 10.2174/0929867324666171006144725 [doi]
PST - ppublish
SO  - Curr Med Chem. 2019;26(6):1002-1018. doi: 10.2174/0929867324666171006144725.