Cancer Immunotherapy: A Preclinical Study of Urinary Bladder Cancer

Bacillus Calmette Guerin (BCG), or attenuated Mycobacterium bovis, is the gold standard of immunotherapy in the clinic to treat superficial bladder cancer. However, setbacks remain due to a high recurrence rate, side effects, and BCG-refractory disease. In this thesis, we explored the use of novel immunotherapeutic agents such as CpG oligodeoxynucleotides (CpG ODNs) or synthetic ODNs containing unmethylated CpG dinucleotides. Since unmethylated CpG motifs are predominant in bacterial but not vertebrate DNA, they function as a “danger signal” leading to a potent immune response.To be able to test various immunotherapeutic agents, we optimized subcutaneous (s.c.), metastatic, and orthotopic models using the murine bladder-49 (MB49) cancer cell line. In the orthotopic model, we show that poly-L-lysine promotes MB49 attachment to the bladder leading to 100% tumor take. In addition, Clorpactin (sodium oxychlorosene) potently enhances adenoviral transduction in the bladder…


The immune system
Innate and adaptive immunity
Pattern recognition receptors
T lymphocyte activation and regulation
Tumor immunology
Theories regarding immune activation
Immune escape mechanisms
Immune responses to tumors
Cancer immunotherapy
The birth of immunotherapy
Types of immunotherapy
Gene transfer vectors
Cellular therap
Immunostimulatory molecules for immunotherapy
Urinary bladder carcinoma
Epidemiology and etiology
Present investigation
Aims of the study
Materials and Methods
Results and discussion
Paper I
Papers II and III
Paper IV
Murine Model
Human Model
Future perspectives

Author: Ninalga, Christina

Source: Uppsala University Library

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