Intratumoral DNA electroporation induces anti-tumor immunity and tumor regression

Radkevich-Brown, Olga; Piechocki, Marie P.; Back, Jessica B.; Weise, Amy; Pilon‐Thomas, Shari; Wei, Wei Zen

doi:10.1007/s00262-009-0760-1

Cited by 19 publications

(17 citation statements)

References 35 publications

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“…The antitumor effectiveness of intratumoral IL-12 electrogene therapy was demonstrated also in other types of cancer, such as colon carcinoma, renal cancer, lymphoma, breast carcinoma and sarcoma mouse tumor models [75][76][77][78][79][80]. Treatment of CT26 colon carcinoma tumors with 3 times repeated intratumoral IL-12 electrogene therapy resulted in significant inhibition of tumor growth.…”

Section: Preclinical Studies With Il-12 Electro-gene Therapymentioning

confidence: 88%

“…These results are in contradiction with other published reports on IL-12 electrogene therapy. The reason for this discrepancy was not addressed by the authors and remains to be elucidated [80]. Recently, intratumoral IL-12 electrogene therapy combined with small interference RNA (siRNA) targeting microphthalmia-associated transcription factor (Mitf) was evaluated in B16 melanoma [99].…”

Section: Il-12 Electrogene Therapy In Combination With Other Therapiesmentioning

confidence: 99%

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Cancer Electrogene Therapy with Interleukin-12

Čemažar¹,

Jarm²,

Serša

2010

CGT

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Electrogene therapy combines administration of plasmid DNA into tissue followed by local application of electric pulses. In electrogene therapy with interleukin-12 (IL-12), different routes of administration, different doses of plasmid DNA and different protocols for delivery of electric pulses were evaluated in numerous preclinical studies. Antitumor effectiveness was tested in different types of primary tumors, distantly growing tumors and induced metastases. Intratumoral IL-12 electrogene therapy has been proved to be very effective in local tumor control, having also a systemic effect. Intramuscular and peritumoral IL-12 electrogene therapy had also a pronounced systemic effect and when combined with other treatment strategies resulted in tumor cures. Antitumor effectiveness of IL-12 electrogene therapy is due to the induction of adaptive immunity and innate resistance and anti-angiogenic action. Translation of preclinical studies into clinical trials in human and veterinary oncology has started with encouraging results that would hopefully lead to further investigation of this therapy, also in combination with other cancer treatment modalities.

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Section: Preclinical Studies With Il-12 Electro-gene Therapymentioning

confidence: 88%

Section: Il-12 Electrogene Therapy In Combination With Other Therapiesmentioning

confidence: 99%

Cancer Electrogene Therapy with Interleukin-12

Čemažar¹,

Jarm²,

Serša

2010

CGT

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“…These effects have been described in melanomas 7–11 , lung carcinomas 12, 13 , fibrosarcomas 14 , pancreatic carcinomas 15 , mammary tumors 16 and colorectal carcinomas 17, 18 . In two studies, antitumor effects were observed after intratumor electrotransfer of an oligonucleotide containing a CpG motif, although each oligonucleotide primarily functioned as an antisense molecule 19, 20 .…”

Section: Introductionmentioning

confidence: 91%

Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas

2013

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Enhanced tumor delivery of plasmid DNA with electric pulses in vivo has been confirmed in many preclinical models. Intratumor electrotransfer of plasmids encoding therapeutic molecules has reached Phase II clinical trials. In multiple preclinical studies, a reduction in tumor growth, increased survival, or complete tumor regression have been observed in control groups in which vector or backbone plasmid DNA electrotransfer was performed. This study explores factors that could produce this antitumor effect. The specific electrotransfer pulse protocol employed significantly potentiated the regression. Tumor regression was observed after delivery of singlestranded or double-stranded DNA with or without CpG motifs in both immunocompetent and immunodeficient mice, indicating the involvement of the innate immune system in response to DNA. In conclusion, this study demonstrated that the observed antitumor effects are not due to a single factor, but to a combination of factors.

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“…We have tested several strategies to trigger tumor immunity in situ . Intratumoral electroporation of D2F2 mammary tumors with cDNA encoding Tetanus toxoid fragment C and IL-12 induced antibody response to Tetanus toxin, T-cell response to endogenous TAA, heavy inflammatory infiltration, partial regression of established tumors and immune memory which protected mice from repeated tumor challenge [80]. These effects are most evident when Tregs are depleted using CD25 mAb, demonstrating a pre-existing, though suppressed immunity to TAA.…”

Section: In Situ Vaccination By Non-surgical Ablationmentioning

confidence: 99%

Evolution of animal models in cancer vaccine development

Wei

Jones

Juhász

et al. 2015

Vaccine

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Advances in cancer vaccine development are facilitated by animal models reflecting key features of human cancer and its interface with host immunity. Several series of transplantable preneoplastic and neoplastic mouse mammary lesions have been used to delineate mechanisms of anti-tumor immunity. Mimicking immune tolerance to tumor-associated antigens (TAA) such as HER2/neu, transgenic mice developing spontaneous mammary tumors are strong model systems for pre-clinical vaccine testing. In these models, HER2 DNA vaccines are easily administered, well-tolerated, and induce both humoral and cellular immunity. Although engineered mouse strains have advanced cancer immunotherapy, basic shortcomings remain. For example, multiple mouse strains have to be tested to recapitulate genetic regulation of immune tolerance in humans. Outbred domestic felines more closely parallel humans in the natural development of HER2 positive breast cancer and their varying genetic background. Electrovaccination with heterologous HER2 DNA induces robust adaptive immune responses in cats. Importantly, homologous feline HER2 DNA with a single amino acid substitution elicits unique antibodies to feline mammary tumor cells, unlocking a new vaccine principle. As an alternative approach to targeted vaccination, non-surgical tumor ablation such as cryoablation induces anti-tumor immunity via in situ immunization, particularly when combined with toll-like receptor (TLR) agonist. As strategies for vaccination advance, non-invasive monitoring of host response becomes imperative. As an example, magnetic resonance imaging (MRI) and positron emission tomography (PET) scanning following administration of tryptophan metabolism tracer [11C]-alpha-methyl-tryptophan (AMT) provides non-invasive imaging of both tumor growth and metabolic activities. Because AMT is a substrate of indoleamine-pyrrole 2,3-dioxygenase (IDO), an enzyme that produces the immune regulatory molecule kynurenine, AMT imaging can provide novel insight of host response. In conclusion, new feline models improve the predictive power of cancer immunotherapy and real-time PET imaging enables mechanistic monitoring of host immunity. Strategic utilization of these new tools will expedite cancer vaccine development.

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Intratumoral DNA electroporation induces anti-tumor immunity and tumor regression

Cited by 19 publications

References 35 publications

Cancer Electrogene Therapy with Interleukin-12

Cancer Electrogene Therapy with Interleukin-12

Electrotransfer of single-stranded or double-stranded DNA induces complete regression of palpable B16.F10 mouse melanomas

Evolution of animal models in cancer vaccine development

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