Radiation therapy combined with<i>Listeria monocytogenes</i>-based cancer vaccine synergize to enhance tumor control in the B16 melanoma model

Lim, Joanne Y.H.; Brockstedt, Dirk G.; Lord, Edith M.; Gerber, Scott A.

doi:10.4161/onci.29028

Cited by 12 publications

(6 citation statements)

References 48 publications

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“…The combination of Lm-based immunotherapy with radiotherapy has shown promise as a synergistic treatment regimen in a preclinical model for melanoma (86). However, there are still challenges to discover the most efficient sequence of treatment administration for both the Lm vaccine and radiotherapy, i.e.…”

Section: Listeria As a Targeted Radionuclide Therapeutic (Trt) Platformmentioning

confidence: 99%

“…However, recent work has found that RT does not solely disrupt tumor cell division but has immunostimulatory effects in the TME (127). RT helps trigger the release of tumor antigens, improve presentation of tumor antigens to T cells, and induces an inflammatory response in the TME that results in elevated IFNg levels and reduced immunosuppression (86,128). However, despite all these attractive features of RT, resistance and recurrence still occur through multiple mechanisms (129).…”

Section: Lm In Combination With Radiotherapymentioning

confidence: 99%

“…However, despite all these attractive features of RT, resistance and recurrence still occur through multiple mechanisms (129). In order to improve the efficacy of RT, a recent study utilized a combination of RT and Lm-OVA in the B16-OVA melanoma model (86). This approach resulted in an increase in the activated T cells infiltrating the TME and a more robust response in the combination therapy than in the use of Lm or RT alone.…”

Section: Lm In Combination With Radiotherapymentioning

confidence: 99%

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Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

2021

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The promise of tumor immunotherapy to significantly improve survival in patients who are refractory to long-standing therapies, such as chemotherapy and radiation, is now being realized. While immune checkpoint inhibitors that target PD-1 and CTLA-4 are leading the charge in clinical efficacy, there are a number of other promising tumor immunotherapies in advanced development such as Listeria-based vaccines. Due to its unique life cycle and ability to induce robust CTL responses, attenuated strains of Listeria monocytogenes (Lm) have been utilized as vaccine vectors targeting both infectious disease and cancer. In fact, preclinical studies in a multitude of cancer types have found Listeria-based vaccines to be highly effective at activating anti-tumor immunity and eradicating tumors. Several clinical trials have now recently reported their results, demonstrating promising efficacy against some cancers, and unique challenges. Development of the Lm-based immunotherapies continues with discovery of improved methods of attenuation, novel uses, and more effective combinatorial regimens. In this review, we provide a brief background of Listeria monocytogenes as a vaccine vector, discuss recent clinical experience with Listeria-based immunotherapies, and detail the advancements in development of improved Listeria-based vaccine platforms and in their utilization.

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Section: Listeria As a Targeted Radionuclide Therapeutic (Trt) Platformmentioning

confidence: 99%

Section: Lm In Combination With Radiotherapymentioning

confidence: 99%

Section: Lm In Combination With Radiotherapymentioning

confidence: 99%

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Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

2021

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“…42 In the B16 murine melanoma tumor model, Lim and colleagues demonstrated that local radiation therapy, followed by Lm vaccination encoding a tumor antigen, led to anti-tumor responses greater than that observed with vaccination or radiation therapy alone. 43 Finally, in clinical trials for patients with pancreatic cancer, Lm encoding a tumor antigen has been used as a booster immunization following a priming immunization with an allogeneic whole cell tumor vaccine, with evidence of clinical activity. 9 Taken together, these findings suggest that there may be a specific advantage of using Lm as a booster vaccine in prime/boost strategies.…”

Section: E1456603-6mentioning

confidence: 99%

Heterologous vaccination targeting prostatic acid phosphatase (PAP) using DNA andListeriavaccines elicits superior anti-tumor immunity dependent on CD4+ T cells elicited by DNA priming

et al. 2018

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. Sipuleucel T, an autologous cell-based vaccine targeting prostatic acid phosphatase (PAP), has demonstrated efficacy for the treatment of advanced prostate cancer. DNA vaccines encoding PAP and live attenuated vaccines have entered clinical trials for patients with prostate cancer, and have advantages in terms of eliciting predominantly Th1-biased immunity. In this study, we investigated whether the immunogenicity and anti-tumor efficacy of a DNA and vaccine, each encoding PAP, could be enhanced by using them in a heterologous prime/boost approach. . Transgenic mice expressing HLA-A2.01 and HLA-DRB1*0101 were immunized alone or with a heterologous prime/boost strategy. Splenocytes were evaluated for MHC class I and II-restricted, PAP-specific immune responses by IFNγ ELISPOTs. Anti-tumor activity to a syngeneic, PAP-expressing tumor line was evaluated.. PAP-specific cellular immunity and anti-tumor activity were elicited in mice after immunization with DNA- or listeria-based vaccines. Greater CD4+ and CD8+ responses, and anti-tumor responses, were elicited when mice were immunized first with DNA and boosted with , but not when administered in the opposite order. This was found to be dependent on CD4+ T cells elicited with DNA priming, and was not due to inflammatory signals by itself or due to B cells serving as antigen-presenting cells for DNA during priming.. Heterologous prime/boost vaccination using DNA priming with boosting may provide better anti-tumor immunity, similar to many reports evaluating DNA priming with vaccines targeting foreign microbial antigens. These findings have implications for the design of future clinical trials.

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“…Most recent studies to analyze pathological mechanisms or innovative treatments have been done on cell culture models in vitro only (1)(2)(3)(4). Preclinical in vivo animal MM models have so far been very rarely reported (5)(6)(7)(8).…”

Section: Introductionmentioning

confidence: 99%

Monitoring of tumor burden in vivo by optical imaging in a xenograft SCID mouse model: evaluation of two fluorescent proteins of the GFP-superfamily

et al. 2018

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Background Mouse models of human-malignant-melanoma (MM) are important tools to study tumor dynamics. The enhanced green fluorescent protein (EGFP) is widely used in molecular imaging approaches, together with optical scanners, and fluorescence imaging. Purpose Currently, there are no data available as to whether other fluorescent proteins are more suitable. The goal of this preclinical study was to analyze two fluorescent proteins of the GFP superfamily under real-time in vivo conditions using fluorescence reflectance imaging (FRI). Material and Methods The human melanoma cell line MeWo was stable transfected with one plasmid: pEGFP-C1 or pDsRed1-N1. We investigated two severe combined immunodeficiency (SCID)-mice groups: A (solid xenografts) and B (xenografts as metastases). After three weeks, the animals were weekly imaged by FRI. Afterwards the mice were euthanized and metastases were imaged in situ: to quantify the cutis-dependent reduction of emitted light, we compared signal intensities obtained by metastases in vivo with signal intensities obtained by in situ liver parenchyma preparations. Results More than 90% of cells were stable transfected. EGFP-/DsRed-xenograft tumors had identical growth kinetics. In vivo the emitted light by DsRed tumors/metastases was much brighter than by EGFP. DsRed metastases were earlier (3 vs. 5 weeks) and much more sensitive detectable than EGFP metastases. Cutis-dependent reduction of emitted light was greater in EGFP than in DsRed mice (tenfold). Autofluorescence of DsRed was lower than of EGFP. Conclusion We established an in vivo xenograft mouse model (DsRed-MeWo) that is reliable, reproducible, and superior to the EGFP model as a preclinical tool to study innovative therapies by FRI under real-time in vivo conditions.

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Radiation therapy combined withListeria monocytogenes-based cancer vaccine synergize to enhance tumor control in the B16 melanoma model

Cited by 12 publications

References 48 publications

Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

Clinical Experience and Recent Advances in the Development of Listeria-Based Tumor Immunotherapies

Heterologous vaccination targeting prostatic acid phosphatase (PAP) using DNA andListeriavaccines elicits superior anti-tumor immunity dependent on CD4+ T cells elicited by DNA priming

Monitoring of tumor burden in vivo by optical imaging in a xenograft SCID mouse model: evaluation of two fluorescent proteins of the GFP-superfamily

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