Anti-tumor effect of DNA-based vaccination and dSLIM immunomodulatory molecules in mice with Ph+ acute lymphoblastic leukaemia

Köchling, Joachim; Prada, Javier; Bahrami, Masoud; Stripecke, Renata; Seeger, Karl; Henze, Günter; Wittig, Burghardt; Schmidt, Manuel

doi:10.1016/j.vaccine.2008.06.094

Cited by 19 publications

(13 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…dSLIM activates the immune system in order to protect against tumorassociated antigens by targeting the TLR9 receptor on certain immune cells (Kochling et al, 2008). As a result of chemotherapy and radiotherapy, tumor-associated antigens are released by cancer cells.…”

Section: Tlr5 7 8 and 9 Agonistsmentioning

confidence: 99%

Roles of toll-like receptors in Cancer: A double-edged sword for defense and offense

et al. 2012

View full text Add to dashboard Cite

Toll-like receptors (TLRs) belong to a class of pattern-recognition receptors that play an important role in host defense against pathogens by recognizing a wide variety of pathogen-associated molecular patterns (PAMPs). Besides driving inflammatory responses, TLRs also regulate cell proliferation and survival by expanding useful immune cells and integrating inflammatory responses and tissue repair processes. TLR signaling, which is centrally involved in the initiation of both innate and adaptive immune responses, has been thought to be restricted to immune cells. However, recent studies have shown that functional TLRs are expressed not only on immune cells, but also on cancer cells, thus implicating a role of TLRs in tumor biology. Increasing bodies of evidence have suggested that TLRs act as a double-edged sword in cancer cells because uncontrolled TLR signaling provides a microenvironment that is necessary for tumor cells to proliferate and evade the immune response. Alternatively, TLRs can induce an antitumor immune response in order to inhibit tumor progression. In this review, we summarize the dual roles of TLRs in tumor cells and, more importantly, delve into the therapeutic potential of TLRs in the context of tumorigenesis.

show abstract

Section: Tlr5 7 8 and 9 Agonistsmentioning

confidence: 99%

Roles of toll-like receptors in Cancer: A double-edged sword for defense and offense

et al. 2012

View full text Add to dashboard Cite

show abstract

“…dSLIMs stimulate cultured peripheral blood mononuclear cells (PBMCs) from healthy donors to secrete Th1 cytokines, including IFNγ, IL-2 and IL-12 230 . Moreover, dSLIMs have been shown to enhance the antileukemic effects of peptide vaccines combined with the granulocyte monocyte colony stimulating factor (GM-CSF), in vivo 231 . Seventeen metastatic colorectal cancer patients receiving dSLIMs in combination with chemotherapy and a peptide vaccine developed no severe toxicity, yet in this setting the adjuvant failed to boost anticancer immune responses 232 .…”

Section: Tlr9 Agonistsmentioning

confidence: 99%

Trial Watch

et al. 2012

View full text Add to dashboard Cite

Toll-like receptors (TLRs) are prototypic pattern recognition receptors (PRRs) best known for their ability to activate the innate immune system in response to conserved microbial components such as lipopolysaccharide and double-stranded RNA. Accumulating evidence indicates that the function of TLRs is not restricted to the elicitation of innate immune responses against invading pathogens. TLRs have indeed been shown to participate in tissue repair and injury-induced regeneration as well as in adaptive immune responses against cancer. In particular, TLR4 signaling appears to be required for the efficient processing and cross-presentation of cell-associated tumor antigens by dendritic cells, which de facto underlie optimal therapeutic responses to some anticancer drugs. Thus, TLRs constitute prominent therapeutic targets for the activation/intensification of anticancer immune responses. In line with this notion, long-used preparations such as the Coley toxin (a mixture of killed Streptococcus pyogenes and Serratia marcescens bacteria) and the bacillus Calmette-Guérin (BCG, an attenuated strain of Mycobacterium bovis originally developed as a vaccine against tuberculosis), both of which have been associated with consistent anticancer responses, potently activate TLR2 and TLR4 signaling. Today, besides BCG, only one TLR agonist is FDA-approved for therapeutic use in cancer patients: imiquimod. In this Trial Watch, we will briefly present the role of TLRs in innate and cognate immunity and discuss the progress of clinical studies evaluating the safety and efficacy of experimental TLR agonists as immunostimulatory agents for oncological indications.

show abstract

“…14). The use of adjuvants or mechanisms that upregulate cell-surface immune activation molecules, improve the intrinsic immunogenicity and therapeutic potential of leukemia cell vaccines (15)(16)(17). Indeed, allogeneic HSCT recipients with advanced high-risk ALL and AML were shown to generate tumorspecific responses and survive longer following treatment with autologous leukemia cells mixed with syngeneic skin fibroblasts expressing CD40L and interleukin (IL)-2 from adenoviral vectors (18).…”

Section: Introductionmentioning

confidence: 99%

Leukemia Cell-Rhabdovirus Vaccine: Personalized Immunotherapy for Acute Lymphoblastic Leukemia

Conrad

Tsang

Maclean

et al. 2013

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: Acute lymphoblastic leukemia (ALL) remains incurable in most adults. It has been difficult to provide effective immunotherapy to improve outcomes for the majority of patients. Rhabdoviruses induce strong antiviral immune responses. We hypothesized that mice administered ex vivo rhabdovirus-infected ALL cells [immunotherapy by leukemia-oncotropic virus (iLOV)] would develop robust antileukemic immune responses capable of controlling ALL.Experimental Design: Viral protein production, replication, and cytopathy were measured in human and murine ALL cells exposed to attenuated rhabdovirus. Survival following injection of graded amounts of ALL cells was compared between cohorts of mice administered g-irradiated rhabdovirus-infected ALL cells (iLOV) or multiple control vaccines to determine key immunotherapeutic components and characteristics. Host immune requirements were assessed in immunodeficient and bone marrow-transplanted mice or by adoptive splenocyte transfer from immunized donors. Antileukemic immune memory was ascertained by second leukemic challenge in long-term survivors.Results: Human and murine ALL cells were infected and killed by rhabdovirus; this produced a potent antileukemia vaccine. iLOV protected mice from otherwise lethal ALL by developing durable leukemiaspecific immune-mediated responses (P < 0.0001), which required an intact CTL compartment. Preexisting antiviral immunity augmented iLOV potency. Splenocytes from iLOV-vaccinated donors protected 60% of na€ ve recipients from ALL challenge (P ¼ 0.0001). Injecting leukemia cells activated by, or concurrent with, multiple Toll-like receptor agonists could not reproduce the protective effect of iLOV. Similarly, injecting uninfected irradiated viable, apoptotic, or necrotic leukemia cells with/without concurrent rhabdovirus administration was ineffective.Conclusion: Rhabdovirus-infected leukemia cells can be used to produce a vaccine that induces robust specific immunity against aggressive leukemia.

show abstract

Anti-tumor effect of DNA-based vaccination and dSLIM immunomodulatory molecules in mice with Ph+ acute lymphoblastic leukaemia

Cited by 19 publications

References 34 publications

Roles of toll-like receptors in Cancer: A double-edged sword for defense and offense

Roles of toll-like receptors in Cancer: A double-edged sword for defense and offense

Trial Watch

Leukemia Cell-Rhabdovirus Vaccine: Personalized Immunotherapy for Acute Lymphoblastic Leukemia

Contact Info

Product

Resources

About