Mediation of Immune Responses to Tumor Antigens by Immune RNA1

2015 ◽  
pp. 163-177
Author(s):  
Yosef H. Pilch
Keyword(s):  
Immune Responses ◽  
Tumor Antigens

scholarly journals Targeting Tumor Antigens to Secreted Membrane Vesicles In vivo Induces Efficient Antitumor Immune Responses

2008 ◽  
Vol 68 (4) ◽  
pp. 1228-1235 ◽  
Author(s):  
Ingrid S. Zeelenberg ◽  
Matias Ostrowski ◽  
Sophie Krumeich ◽  
Angélique Bobrie ◽  
Carolina Jancic ◽  
...  
Keyword(s):  
Immune Responses ◽  
Tumor Antigens ◽  
Membrane Vesicles

scholarly journals Natural Killer Dendritic Cells Enhance Immune Responses Elicited byα-Galactosylceramide-Stimulated Natural Killer T Cells

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Sung Won Lee ◽  
Hyun Jung Park ◽  
Nayoung Kim ◽  
Seokmann Hong
Keyword(s):  
T Cells ◽  
Dendritic Cells ◽  
Immune Responses ◽  
Natural Killer ◽  
Immune Cells ◽  
Tumor Antigens ◽  
Nkt Cells ◽  
Innate Immune ◽  
Innate Immune Cells ◽  
Natural Killer T

Natural killer dendritic cells (NKDCs) possess potent anti-tumor activity, but the cellular effect of NKDC interactions with other innate immune cells is unclear. In this study, we demonstrate that the interaction of NKDCs and natural killer T (NKT) cells is required for the anti-tumor immune responses that are elicited byα-galactosylceramide (α-GC) in mice. The rapid and strong expression of interferon-γby NKDCs afterα-GC stimulation was dependent on NKT cells. Various NK and DC molecular markers and cytotoxic molecules were up-regulated followingα-GC administration. This up-regulation could improve NKDC presentation of tumor antigens and increase cytotoxicity against tumor cells. NKDCs were required for the stimulation of DCs, NK cells, and NKT cells. The strong anti-tumor immune responses elicited byα-GC may be due to the down-regulation of regulatory T cells. Furthermore, the depletion of NKDCs dampened the tumor clearance mediated byα-GC-stimulated NKT cellsin vivo. Taken together, these results indicate that complex interactions of innate immune cells might be required to achieve optimal anti-tumor immune responses during the early stages of tumorigenesis.

Correlation of specific immune responses with survival in melanoma patients with distant metastases receiving polyvalent melanoma cell vaccine.

1998 ◽  
Vol 16 (9) ◽  
pp. 2913-2920 ◽  
Author(s):  
E C Hsueh ◽  
R K Gupta ◽  
K Qi ◽  
D L Morton
Keyword(s):  
Immune Response ◽  
Immune Responses ◽  
Melanoma Cell ◽  
Tumor Antigens ◽  
Univariate Analysis ◽  
Distant Metastases ◽  
Skin Tests ◽  
Delayed Type Hypersensitivity ◽  
Cell Vaccine ◽  
Immune Competence

PURPOSE The mechanisms that underlie the clinical efficacy of melanoma vaccines are not well understood. We hypothesized that the type and strength of the immune response generated by CancerVax (John Wayne Cancer Institute, Santa Monica, CA), a polyvalent melanoma cell vaccine (PMCV), might be correlated with its effect on overall survival (OS). PATIENTS AND METHODS Seventy-seven patients began PMCV therapy after complete surgical resection of distant metastatic melanoma. During the first two treatments, PMCV was administered with bacille Calmette-Guerin (BCG). Blood was drawn at 0, 2, 4, 8, and 12 weeks to measure serum titers of immunoglobulin G (IgG) and IgM antibodies against a tumor-associated 90-kd glycoprotein antigen (TA90) expressed on most melanoma cells, including those of PMCV. Cellular immune response to PMCV was assessed by delayed-type hypersensitivity (DTH). General immune competence was assessed by skin tests to purified protein derivative (PPD), mumps, and candida. RESULTS Median follow-up time was 31.5 months. Within the first 12 weeks of PMCV immunotherapy, there was a significant increase in the anti-TA90 IgM (P=.0001) and IgG titers (P=.0001), and in the DTH response to PMCV (P=.0001). Univariate analysis showed that high anti-TA90 IgM titer and strong PMCV-DTH were associated with improved survival (P=.051 and .0173, respectively), whereas elevated anti-TA90 IgG was correlated with decreased survival (P=.0119). Multivariate analysis considering clinical variables and PMCV immune responses identified anti-TA90 IgM, anti-TA90 IgG, and PMCV-DTH as significant independent variables influencing survival following PMCV immunotherapy (P=.0342, .0105, and .0082, respectively). These responses to PMCV were not correlated with immune responses to BCG and therefore were not a manifestation of general immune competence for responses to unrelated antigens. The median survival time and 5-year survival rate were more than 76 months and 75%, respectively, if both anti-TA90 IgM and PMCV-DTH responses were strong (> or = 800 and > or = 7 mm, respectively; n=29); 32 months and 36%, respectively, if only one response was strong (n=35); and 19 months and 8%, respectively, if neither was strong (n=13) (P < .0001). CONCLUSION PMCV induces both humoral and cell-mediated immune responses to melanoma-associated tumor antigens, the type and strength of which appear to be directly related to its therapeutic efficacy.

Therapeutic Antimyeloma Effect of Dendritic-Tumor Cells Hybrids Transduced with Adenovirus Encoding CD40L.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1709-1709
Author(s):  
Eva Alvarez ◽  
Esther Moga ◽  
Jorge Sierra ◽  
Javier Briones
Keyword(s):  
T Cell ◽  
Immune Responses ◽  
Tumor Cells ◽  
Antitumor Effect ◽  
Tumor Antigens ◽  
Recombinant Adenovirus ◽  
Lymphoid Tissues ◽  
Term Survival ◽  
Mhc Ii

Abstract Dendritic cells (DCs) are the main antigen presenting cells and play a pivotal role in the stimulation of T-cell immune responses. DCs cultured in the presence of a single tumor antigen can elicit an immune response against tumor cells expressing that antigen. However, simultaneous use of several tumor antigens may be advantageous since polyclonal activation of T cells against different tumor antigens may be a better approach to eradicate tumor cells. In this sense, fusions of dendritic and tumor cells (FCs) show a broad spectrum of tumor antigens, both known and unidentified, to be presented by class I and II MHC. Although prophylactic vaccines were successful in murine models, the results in the therapeutic setting have been unsatisfactory. We hypothesised that enhancing costimulation of FCs would help to break tumor tolerance once the tumor is established. To this purpose, we transduced FCs with a recombinant adenovirus encoding CD40L (AdvCD40L or AdvGFP as control) and we studied the therapeutic antitumoral effect of the administration of FC-CD40L in a murine model of myeloma. DCs obtained from day 7-bone marrow cultures of Balb/c mice were fused with tumor cells, a syngeneic murine myeloma cell line (4TOO). FCs hybrids were generated with PEG and selected after culturing in HAT medium plus GM-CSF for 7 days. FC were quantified by determining the percentage of cells that coexpress specific DC (CD11c) and tumor markers (CD138). Mean fusion efficiency was 30% (20–40%) and FCs expressed moderate levels of CD80, CD83, CD86, CD54, CD40 and MHC II and did not express CD40L. FC-CD40L showed a significant increase of expression of costimulatory molecules (CD80, CD86, CD54, and MHC II) compared to FC-GFP (p=0.011). Moreover, in a syngeneic mixed lymphocyte reaction, FC-CD40L induced a two-fold higher T-cell proliferation than FC-GFP or FC alone. In addition, FC-CD40L had improved migration to lymphoid tissues, preferentially to spleen, in comparison with FC-GFP (2.8% versus 1.6%). The antitumor effect of FC-CD40L was analyzed in vivo. Mice (n=10 per group) were injected i.v. with 2.5×105 tumor cells and treated with irradiated FC, FC-GFP or FC-CD40L (1×106 cells each) on days 2, 6 and 10 after tumor challenge. 40% of mice treated with FC-CD40L had long-term survival (&gt;120 days). In contrast, all of mice treated with FC or FC-GFP died between days 25 and 35 (p=0.012). In parallel, treatment with mixed cells (not fused DC+ tumor cells), mix transduced with AdvGFP, or mix transduced with AdvCD40L did not provide any significant antitumor effect. We conclude that FCs transduced with AdvCD40L better stimulate in vitro and in vivo immune responses than FC alone and may provide a new strategy for treating patients with multiple myeloma or lymphoma.

scholarly journals Cancer Vaccines: Adjuvant Potency, Importance of Age, Lifestyle, and Treatments

2021 ◽  
Vol 11 ◽  
Author(s):  
Stefania Cuzzubbo ◽  
Sara Mangsbo ◽  
Divya Nagarajan ◽  
Kinana Habra ◽  
Alan Graham Pockley ◽  
...  
Keyword(s):  
Immune Responses ◽  
Cancer Vaccines ◽  
Tumor Antigens ◽  
Careful Consideration ◽  
Immune Functions ◽  
Mineral Salts ◽  
Functional Changes ◽  
Multiple Tumor ◽  
Novel Technologies

Although the discovery and characterization of multiple tumor antigens have sparked the development of many antigen/derived cancer vaccines, many are poorly immunogenic and thus, lack clinical efficacy. Adjuvants are therefore incorporated into vaccine formulations to trigger strong and long-lasting immune responses. Adjuvants have generally been classified into two categories: those that ‘depot’ antigens (e.g. mineral salts such as aluminum hydroxide, emulsions, liposomes) and those that act as immunostimulants (Toll Like Receptor agonists, saponins, cytokines). In addition, several novel technologies using vector-based delivery of antigens have been used. Unfortunately, the immune system declines with age, a phenomenon known as immunosenescence, and this is characterized by functional changes in both innate and adaptive cellular immunity systems as well as in lymph node architecture. While many of the immune functions decline over time, others paradoxically increase. Indeed, aging is known to be associated with a low level of chronic inflammation—inflamm-aging. Given that the median age of cancer diagnosis is 66 years and that immunotherapeutic interventions such as cancer vaccines are currently given in combination with or after other forms of treatments which themselves have immune-modulating potential such as surgery, chemotherapy and radiotherapy, the choice of adjuvants requires careful consideration in order to achieve the maximum immune response in a compromised environment. In addition, more clinical trials need to be performed to carefully assess how less conventional form of immune adjuvants, such as exercise, diet and psychological care which have all be shown to influence immune responses can be incorporated to improve the efficacy of cancer vaccines. In this review, adjuvants will be discussed with respect to the above-mentioned important elements.

scholarly journals Immune Checkpoints and CAR-T Cells: The Pioneers in Future Cancer Therapies?

2020 ◽  
Vol 21 (21) ◽  
pp. 8305
Author(s):  
Negar Hosseinkhani ◽  
Afshin Derakhshani ◽  
Omid Kooshkaki ◽  
Mahdi Abdoli Shadbad ◽  
Khalil Hajiasgharzadeh ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Side Effects ◽  
Immune Responses ◽  
Gene Editing ◽  
Tumor Antigens ◽  
Immune Checkpoints ◽  
Car T Cells ◽  
Ample Opportunity ◽  
Car T

Although the ever-increasing number of cancer patients pose substantial challenges worldwide, finding a treatment with the highest response rate and the lowest number of side effects is still undergoing research. Compared to chemotherapy, the relatively low side effects of cancer immunotherapy have provided ample opportunity for immunotherapy to become a promising approach for patients with malignancy. However, the clinical translation of immune-based therapies requires robust anti-tumoral immune responses. Immune checkpoints have substantial roles in the induction of an immunosuppressive tumor microenvironment and tolerance against tumor antigens. Identifying and targeting these inhibitory axes, which can be established between tumor cells and tumor-infiltrating lymphocytes, can facilitate the development of anti-tumoral immune responses. Bispecific T-cell engagers, which can attract lymphocytes to the tumor microenvironment, have also paved the road for immunological-based tumor elimination. The development of CAR-T cells and their gene editing have brought ample opportunity to recognize tumor antigens, independent from immune checkpoints and the major histocompatibility complex (MHC). Indeed, there have been remarkable advances in developing various CAR-T cells to target tumoral cells. Knockout of immune checkpoints via gene editing in CAR-T cells might be designated for a breakthrough for patients with malignancy. In the midst of this fast progress in cancer immunotherapies, there is a need to provide up-to-date information regarding immune checkpoints, bispecific T-cell engagers, and CAR-T cells. Therefore, this review aims to provide recent findings of immune checkpoints, bispecific T-cell engagers, and CAR-T cells in cancer immunotherapy and discuss the pertained clinical trials.

Abstract LB-195: Immune responses against cancer stem cell-specific tumor antigens and tumor microenvironment

2012 ◽  
Author(s):  
Toshihiko Torigoe ◽  
Yoshihiko Hirohashi ◽  
Reina Morita ◽  
Satoshi Nishizawa ◽  
Kazuyo Yasuda ◽  
...  
Keyword(s):  
Stem Cell ◽  
Tumor Microenvironment ◽  
Immune Responses ◽  
Cancer Stem Cell ◽  
Tumor Antigens ◽  
Specific Tumor

TLR-9 Activated Lymphoma B Cells Induce Anti-Tumor Immunity in a Murine Model

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 4992-4992
Author(s):  
Matthew J. Goldstein ◽  
Joshua Brody ◽  
Ronald Levy
Keyword(s):  
B Cells ◽  
Immune Responses ◽  
Tumor Cells ◽  
Tumor Immunity ◽  
Tumor Antigens ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Cell Vaccine ◽  
Tumor Challenge ◽  
Whole Cell Vaccine

Abstract Background: Tumor vaccines typically combine unique, tumor antigens with immune stimulants in an effort to elicit a tumor-specific immune response. In prior work we have described a vaccination maneuver that combines cytotoxic chemotherapy to release tumor antigens with intra-tumor injection of a Toll-like Receptor 9 (TLR9) ligand, CpG oligonucleotide (Li and Levy, J. Immunology, 2007). In this therapy, CpG can activate both host antigen presenting cells as well as the tumor itself. Stimulation of tumor B cells through TLR9 induces up-regulation of immune co-stimulatory molecules including CD80, CD86, and CD40 as well as increasing expression of MHC Class I and II. We have now developed an alternative vaccination approach in which B cell lymphoma tumor cells are stimulated with CpG ex vivo and administered as a whole-cell vaccine. Methods: A20 B cell lymphoma tumor cells were incubated with CpG for 72 hours, irradiated, and administered to naïve Balb/C mice. The complete vaccination regimen included six doses of 1×106 cells administered daily at a sub-cutaneous (s.c.) site. Vaccine-induced immune responses were assessed by measuring IFN-γ expression of peripheral blood lymphocytes (PBLs) in response to co-culture with A20 tumor cells. Tumor protection studies were conducted by challenging vaccinated mice with a lethal dose of 10×106 A20 tumor cells. Anti-tumor immunity generated by vaccination was also tested in adoptive cell transfer studies. Results: Sub-cutaneous vaccination with CpG-stimulated, whole-cell vaccine induces robust anti-tumor T cell immunity comparable to that induced by intra-tumor vaccination with CpG. This immunizing effect was dependent on tumor cell activation, since native tumor cells were less efficient at inducing anti-tumor immune responses. Both CD4+ and CD8+ T cells participated in this response. Mice vaccinated with this regimen were protected against tumor challenge. Splenocytes from vaccine-primed donors were adoptively transferred into irradiated, syngeneic recipients. These ‘immunotransplanted’ recipients had even greater immune protection against tumor challenge than the directly vaccinated donor mice. Conclusions: We have developed a vaccination approach that takes advantage of the antigen presentation capability of malignant B cells. Vaccination with CpG-activated lymphoma cells induced anti-tumor immune responses that were further enhanced by adoptive transfer of immune cells into lymphodepleted recipients. These vaccine maneuvers are directly translatable into therapeutic, human clinical trials.

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