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Bacteria as a Therapeutic Approach in Cancer Therapy

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Bacteria and Cancer

Abstract

In the wake of growing global burden of cancer, newer cancer prevention and control modalities are being explored. One such novel experimental strategy is the implication of natural and genetically modified non-pathogenic bacterial species as potential antitumor agents. This therapy is based on the fact that live, attenuated or genetically modified non-pathogenic bacterial species are capable of multiplying selectively in tumours and inhibiting their growth. Moreover due to their selectivity for tumour tissues, these bacteria and their spores also serve as ideal vectors for delivering therapeutic proteins to tumours. Bacterial toxins too have been explored for their anti-cancer potential. Although the oncolytic potential of bacteria was recognized several hundred years back yet the bacterial therapy failed to establish because of certain drawbacks associated with it like toxicity, lack of specificity and inconvenient administration of bacteria. However the emergence of gene therapy and recombinant DNA technology has revived the interest in bacterial therapy and a variety of applications employing bacteria have been investigated. Out of these, the most potential and promising strategies are bacteria based gene-directed enzyme prodrug therapy, anaerobic bacteria vector-mediated cancer therapy and immunotherapy. These therapies have demonstrated significant efficacy in preclinical studies and some are currently under clinical investigation.

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Abbreviations

5FC:

5-fluorocytosine

5FU:

5-fluorouracil

ALL:

Acute lymphoblastic leukaemia

AMP:

Adenosine monophosphate

BCG:

Bacillus Calmette-Guerin

BoNT:

Botulinum neurotoxin

BR96 sFv-PE40:

Single-chain immunotoxin. SGN-10 is composed of the fused gene products encoding the translocating and ADP-ribosylating domains of Pseudomonas exotoxin (PE40) and the variable heavy (V(H)) and variable light (V(L)) regions of BR96 monoclonal antibody

CD:

Cytosine deaminase

CDTs:

Cytolethal distending toxins

Cif:

Cycle inhibiting factor

CMV:

Cytomegalovirus

CNF:

Cytotoxic necrotizing factor

COBALT:

Combination bacteriolytic therapy

CPE:

Clostridium perfringens enterotoxin

CPE-R:

CPE receptor

CPG2:

Carboxypeptidase G2

DCA:

Dichloroacetate

DNA:

Deoxyribonucleic acid

DT:

Diphtheria toxin

EF2:

Elongation factor-2

EGF:

Epidermal growth factor

EHEC:

Enterohaemorrhagic E. coli

EPEC:

Enteropathogenic E. coli

erb-38:

A recombinant immunotoxin that targets the erbB2 receptor

G-CSF:

Granulocyte colony stimulating factor

HA22:

(CAT-8015) is an immunotoxin composed of an anti-CD22 variable fragment linked to a 38 kDa truncated protein derived from Pseudomonas exotoxin A.

HAMLET:

Human alpha-lactalbumin made lethal to tumour cells

HB-EGF:

Heparin-binding epidermal growth factor like growth factor

hGM-CSF:

Human granulocyte-macrophage-colony stimulating factor

hIL-12:

Human interleukin-12

HSVTK:

Herpes simplex virus thymidine kinase

IL13-PE38QQR:

Cintredekin besudotox

IL-3:

Interleukin-3

IL-4:

Interleukin-4

IL-4-PE38KDEL:

A chimeric protein composed of circularly permuted IL-4 and a truncated form of Pseudomonas exotoxin (PE), into recurrent malignant high-grade gliomas

IL4-P:

Aeruginosa exotoxin (IL4-PE NBI-3001), tumour growth factor (TGF) alpha-P. aeruginosa exotoxin (TP-38), IL13-P. aeruginosa exotoxin (IL13-PE38), and transferrin-C. diphtheriae toxin (TransMID(trade mark), Tf-CRM107

IL4-PE:

Interleukin-4-Pseudomonas exotoxin

LMB-1:

Is composed of monoclonal antibody B3 chemically linked to PE38 a genetically engineered form of Pseudomonas exotoxin

LMB-2:

CD25-directed immunotoxin

LMB-2:

Recombinant immunotoxin anti-Tac(Fv)-PE38

Mab:

Monoclonal antibody

mGM-CSF:

granulocyte-macrophage-colony stimulating factor

mIL-12:

Murine interleukin 12

NBI-3001:

IL-4 Pseudomonas exotoxin protein

NR:

Nitroreductase

OVB3-PE:

An immunotoxin composed of a murine monoclonal antibody reactive with human ovarian cancer and conjugated to Pseudomonas exotoxin (PE)

PE38:

Is a 38-kDa derivative of the 66-kDa Pseudomonas exotoxin (PE)

TAPET:

Tumour Amplified Protein Expression Therapy

TAPET-CD, VNP20029:

VNP20029genetically modified Salmonella typhimurium expressing cytosine deaminase

Tf:

Transferrin

Tf-CRM 107:

Transferrin-DT conjugate

TGF-α:

Transforming growth factor a

TNF-α:

Tumour necrosis factor α

TP-38:

A recombinant chimeric targeted toxin composed of the EGFR binding ligand TGF-alpha and a genetically engineered form of the Pseudomonas exotoxin PE-38

TP40:

Transforming growth factor alpha-Pseudomonas exotoxin-40

VEGF:

Vascular endothelial growth factor

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  1. Department of Pharmacology, Postgraduate Institute of Medical Education & Research, Research Block B, 4th Floor, Room no 4043, Chandigarh, 160012, India

    Sazal Patyar, Ajay Prakash & Bikash Medhi

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  2. Ajay Prakash
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  3. Bikash Medhi
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Correspondence to Bikash Medhi .

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  1. Vinay Nagar 2C, Gwalior, 474012, Madhya Pradesh, India

    Abdul Arif Khan

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© 2012 Springer Science+Business Media B.V.

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Patyar, S., Prakash, A., Medhi, B. (2012). Bacteria as a Therapeutic Approach in Cancer Therapy. In: Khan, A. (eds) Bacteria and Cancer. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-2585-0_8

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