Treatment of solid tumours in children with tumour-lysate-pulsed dendritic cells

Geiger, James D.; Hutchinson, Raymond J.; Hohenkirk, Lyndon F.; McKenna, Elizabeth A.; Chang, Alfred E.; Mulé, James J.

doi:10.1016/s0140-6736(00)02762-8

Cited by 96 publications

(63 citation statements)

References 5 publications

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“…Immunotherapy directed against other tumors broadly falls into 2 categories: one is to target defined antigens such as overexpressed self antigens (Her2/neu, CEA, muc-1) 238,239 and mutant oncoproteins (bcr-abl, p53, mutant ras) and another is to use crude antigenic preparations derived from autologous tumor lysates, 240 peptides eluted with acid from cells, 241 tumor-derived RNA or heat shock proteins. Injection of tumor lysate-pulsed DCs led to marked tumor regression in a child with metastatic fibrosarcoma and substantial tumor burden.…”

Section: Other Tumorsmentioning

confidence: 99%

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Active immunization against cancer with dendritic cells: The near future

2001

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DCs 1 are antigen-presenting cells that regulate several components of the immune system. The mature or terminal stage of DC development induces specific T-cell immunity and resistance to experimental tumors in vivo. However, DC maturation is induced by inflammatory and microbial stimuli, so it is unlikely that mature DCs normally present antigens from tumor cells in cancer patients. Accordingly, clinical studies have begun in which DCs are generated ex vivo, charged with tumor antigens, exposed to maturation stimuli and reinfused to immunize patients. This approach has the potential to control responses to cancer antigens in a specific and nontoxic manner, in both vaccination and therapeutic settings.DCs can mobilize several immune resistance mechanisms. These include CD8ϩ CTLs, CD4 ϩ helper T cells, NK and NKT cells. Each of these lymphocytes recognizes targets through a distinct mechanism and has the capacity to kill tumor cells and release valuable protective cytokines like IFN-␥. CD4 ϩ T cells also provide essential help for the expansion and maintenance of CD8 ϩ cytolytic cells, while NK and NKT cells can eliminate targets that dampen presentation on MHC class I to escape CTL recognition. The stimulation and concerted action of these classes of lymphocytes can now be studied directly in patients, using ex vivo-derived DCs.Several findings have emerged from studies of healthy volunteers who have been immunized with DCs charged with model antigens, KLH protein and influenza virus matrix peptide. Mature DCs elicit a polarized Th1 type of CD4 T-cell response, only a single injection being required. Vaccination with antigen-bearing DCs also markedly improves the functional affinity of CD8 ϩ T cells. These findings are important in the context of immunotherapy because Th1 cells are more efficient helper cells in experimental models of viral infection and tumors, while high-affinity CTLs should improve recognition of tumor-derived peptides. An important caution also has surfaced when DCs are not adequately differentiated. Immature DCs can silence adaptive T-cell responses, e.g., by inducing IL-10 -producing, T-reg cells.DC-based active immunization does not result in major shortterm toxicity in healthy subjects or cancer patients. Tumor-specific T-cell responses have been induced and detected in fresh blood specimens without the need for restimulation in vitro. However, the immune responses observed in the first protocols are still smaller than those seen naturally in acute viral infections. Occasional clinical regressions have been noted in these initial feasibility studies, particularly in melanomas, pediatric tumors, lymphomas, prostate cancers and renal cell cancers. This information, coupled with progress in DC biology, suggests many ways to improve the efficacy of this new therapy. Some relevant topics include antigen loading and DC maturation procedures, frequency and route of DC injection, efficiency of DC homing to lymphoid tissues and their longevity once there and the role of distinct DC subsets. A val...

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Section: Other Tumorsmentioning

confidence: 99%

“…Injection of tumor lysate-pulsed DCs led to marked tumor regression in a child with metastatic fibrosarcoma and substantial tumor burden. 240 …”

Section: Other Tumorsmentioning

confidence: 99%

Active immunization against cancer with dendritic cells: The near future

2001

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“…One Phase I clinical study using DCs against solid tumors in children, including osteosarcoma, has been reported. In this series, one patient with metastatic fibrosarcoma demonstrated a strong positive response without obvious toxic side effects [20]. The other clinical trial of DC vaccination was for chondrosarcoma.…”

Section: Dendritic Cell Immunotherapymentioning

confidence: 79%

Cryoimmunology for malignant bone and soft-tissue tumors

et al. 2011

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“…A number of clinical trials are currently underway studying DCs in a variety of tumors (43). One clinical phase-I study using DCs against solid tumors in children including osteosarcoma has been reported (44). In this series, one patient with metastatic fibrosarcoma demonstrated strong positive response without obvious toxic side effects.…”

Section: Monocyte Lineage Constitutes a Complex System Of Professionamentioning

confidence: 88%

Osteosarcoma: Current status of immunotherapy and future trends (Review)

Mori¹,

Rédini²,

Cherrier³

et al. 2006

Oncol Rep

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Abstract. Osteosarcoma is the most common primary bone tumor and represents a major therapeutic challenge in medical oncology. While the use of aggressive chemotherapy has drastically improved the prognosis of the patients with nonmetastatic osteosarcomas, the very poor prognosis of patients with metastasis have led to the exploration of new, more effective and less toxic treatments, such as immunotherapy for curing osteosarcoma. Compared to the numerous reports describing successful immunotherapy for other solid tumors, the number of reports concerning immunotherapy for osteosarcoma is low. However, this therapeutic strategy opens new areas for the treatment of osteosarcoma. In this review, the reasons for delay and all elements essential to develop immunotherapy concerning osteosarcoma are defined. Several pieces of evidence strongly support the potential capability of new therapies such as cellular therapy and gene therapy to eradicate osteosarcoma. Thus, clinical human trials using peptides, cytokines and dendritic cells have been performed. Tumor-infiltrating lymphocytes and some tumor antigens have been identified in osteosarcoma and resulted in an important breakthrough in cellular immunotherapy. Also, RANKL/RANK/OPG, the key regulator of bone metabolism, is a hot spot in this field as therapeutic tools. Immunotherapy for osteosarcomas has great potential, promising improvement in the survival rate and better quality of life for the patients.

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Treatment of solid tumours in children with tumour-lysate-pulsed dendritic cells

Cited by 96 publications

References 5 publications

Active immunization against cancer with dendritic cells: The near future

Active immunization against cancer with dendritic cells: The near future

Cryoimmunology for malignant bone and soft-tissue tumors

Osteosarcoma: Current status of immunotherapy and future trends (Review)

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