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O Ito

Publications and source records attributed to O Ito.

At least 91 records · Page 5Linked to original sources
PubMed1996

Periarticular ectopic calcinosis probably due to 1 alpha-OH-vitamin D3 therapy, and successful treatment with bisphosphonate compound in a patient with systemic lupus erythematosus.

We describe the case of a 25-year-old woman who developed soft tissue ectopic nephritis. Ectopic calcinosis rarely occurs in systemic lupus erythematosus (SLE) patients. This is the first detailed case report of metastatic ectopic calcinosis, one of two categories of ectopic calcinosis, probably due to 1 alpha-OH-vitamin D3 therapy. We administered disodium 3-amino-1-hydroxypropylidene-1, 1-bisphosphonate pentahydrate, a second-generation bisphosphonate, to decrease the patient's serum calcium level, and subsequently observed a dramatic decrease in severity of the ectopic calcinosis along with decreases in both the serum calcium level and the (serum calcium level)x(serum phosphate level) index. We suggest that 1 alpha-OH vitamin D3 should be used in cases of lupus nephritis with great caution.

Adult↗
PubMed1995

The involvement of transforming growth factor beta in the impaired antitumor T-cell response at the gut-associated lymphoid tissue (GALT).

We studied the antitumor immune response in gut-associated lymphoid tissue (GALT), which is the tolerance-inducing site for numerous dietary antigens. The mice inoculated with colon 26 carcinoma (C-26) into the subserosal space of the cecum (i.c.) showed a more rapid tumor growth than did the mice inoculated s.c. with C-26 into the flank. In addition, the serum of the i.c. C-26-inoculated mice showed a more potent suppressive activity, and their plasma contained a higher level of transforming growth factor than the s.c. C-26-inoculated mice. We also evaluated the tumor-specific T-cell response in the GALT by utilizing B7-transfected P815 mastocytoma (B7/P815). The rejection of i.c. inoculated B7/P815 was delayed compared to that of the s.c. inoculated B7/P815. The draining axillary lymph node (LN) cells of the s.c. B7/P815-inoculated mice exhibited a CD4+ T-cell-dependent proliferative response to in vitro restimulation, whereas the draining mesenteric LN cells of the i.c. B7/P815-inoculated mice exhibited no apparent response even with the addition of interleukin 2. However, such draining mesenteric LN cells did produce higher levels of interleukin 2 and transforming growth factor beta than the draining axillary LN without any stimulation, and their production of such cytokines depend on the CD4+ and CD8+ cells, respectively. Collectively, our results suggest the possibility that the impaired antitumor T-cell response in the GALT may be attributed to "bystander suppression" by TGF-beta-producing CD8+ T cells.

Animals↗
PubMed1995

Marked detergents effects on safranine T-mediated photo-induced electron transfer in cytochrome P-450 1A2.

Cytochrome P-450 accepts electrons from electron transfer proteins to facilitate monooxidation reactions. It is suggested that basic amino acids such as Lys and Arg on the P-450 molecular surface interact with acidic amino acids such as Glu and Asp of the electron transfer protein. Safranine T is a basic compound which mediates electron transfer with illumination. It was found with flash photolysis that an electron from photo-reduced safranine T quickly reaches the heme iron of cytochrome P-450 1A2 (P-450 1A2). The photo-induced reduction kinetics of P-450 1A2 were analyzed by the Runge-Kutta method on the second order assumption. The electron-transfer rate constant from safranine T to P-450 1A2 was 2.1 x 10(6) M-1s-1. The rate constant was remarkably increased up to 3.1 x 10(8) M-1s-1 by adding cholic acid, while that was drastically reduced down to 3.5 x 10(4) M-1s-1 by adding Emulgen 913. The electron-transfer rate of a His163-Glu mutant, which has a 40 mV lower redox potential than that of the wild type, was the same as that of the wild type in the absence of the detergents, although the reduced fraction of the mutant was 30% lower than that of the wild type. The electron-transfer rate of the mutant also changed significantly by adding the detergents in the same way as the wild type. Based on these results, together with optical absorbance and fluorescence data, we discuss the inter- and intramolecular electron-transfer mechanism of P-450 1A2.

Animals↗
PubMed1995

The antitumor activity induced by the in vivo administration of activated B cells bound to anti-CD3 monoclonal antibody.

We examined the immunotherapeutic ability of activated B cells which bound to anti-CD3 monoclonal antibody (mAb) to enhance antitumor T cell immunity in vivo. A flow cytometric analysis revealed that LPS (lipopolysaccharide)-activated B cells (LPS blasts) expressed Fc receptor (FcR) which can bind to anti-CD3 mAb. LPS blasts were also stained with CTLA-4Ig, which can bind to costimulation molecules with high affinity, which suggested that LPS blasts expressed costimulation molecules on their surface. In an in vitro assay, T cells remarkably proliferated in the presence of LPS blasts and soluble anti-CD3 mAb, whereas this proliferation was blocked by the addition of CTLA-4Ig. In a model of metastasis established by the intravenous inoculation of melanoma cells, the in vivo administration of LPS blasts incubated with anti-CD3 mAb and followed by treatment with polyethylene glycol, to reinforce the binding, induced a low but significant antitumor activity against melanoma. The antitumor activity induced by the in vivo administration of LPS blasts which bound to anti-CD3 mAb was also detected in the spontaneously established model of metastasis. These results therefore suggest that the in vivo administration of activated B cells which bound to anti-CD3 mAb was able to enhance the antitumor T cell response against metastatic melanoma.

Animals↗
PubMed1995

Specific antitumor activity of tumor-infiltrating lymphocytes expanded first in a culture with both anti-CD3 monoclonal antibody and activated B cells and then in a culture with interleukin-2.

In order to expand tumor-infiltrating lymphocytes (TIL) efficiently and in order to use them for immunotherapy, we utilized lipopolysaccharide-activated B cells (LPS blasts) as costimulatory-signal-providing cells in an in vitro culture system. TIL, prepared from subcutaneously inoculated B16 melanoma, failed to expand when cultured with anti-CD3 monoclonal antibody (mAb) alone followed by a low dose of interleukin(IL)-2. In contrast, such TIL did expand efficiently in culture with both anti-CD3 mAb and LPS blasts followed by culture with IL-2. These findings suggest that the presence of LPS blasts in the initial culture was essential for the cell expansion. The expansion of TIL was partially blocked by the addition of CTLA4 Ig, which is an inhibitor of costimulatory molecules such as CD80 and CD86, and was almost blocked by the addition of anti-(Fc receptor gamma II)mAb. These findings thus indicate that such molecules, in conjunction with the receptor on the LPS blasts, participate in the efficient expansion of TIL. The B16-derived TIL, which expanded in our culture system, were predominantly CD8+ T cells and showed a higher level of cytolytic activity against B16 melanoma than either lymphokine-activated killer cells or TIL cultured with a high dose of IL-2. In addition, the in vitro expanded B16-derived TIL produced interferon gamma, but not IL-4, in response to B16 melanoma. What is more important, the adoptive transfer of such TIL had a significant antitumor effect against pulmonary metastasis in B16 melanoma, even without the concurrent administration of IL-2. Collectively, our results thus indicate the therapeutic efficacy of the protocol presented here for antitumor immunotherapy with TIL.

Abatacept↗
PubMed1995

Acceleration of 13C-labelled photosynthate partitioning from leaves to panicles in rice plants exposed to chronic ozone at the reproductive stage.

To investigate the effects of low (0.05 micromol/mol) and relatively low (0.10 micromol/mol) concentrations of ozone on photoassimilate partitioning, rice plants grown in a water culture were fed with (13)C-labelled carbon dioxide at the reproductive stage in an assimilation chamber with constant concentration of (12)CO(2) and (13)CO(2). Rice plants were exposed to ozone 4 weeks before and 3 weeks after (13)CO(2) feeding. The dry weight of whole plants decreased with increasing ozone concentration, whereas net photosynthetic rate (apparent CO(2) uptake per unit leaf area) was unaffected, compared with the control, at the time of (13)CO(2) feeding. Dry matter distribution into leaf sheaths and culms was reduced more than that into leaf blades by ozone exposure. Although panicle dry weight per plant was reduced by ozone, the percentage of panicle dry weight to the whole plant tended to increase considerably. Exposure to ozone accelerated translocation of (13)C from source leaves to other plant parts. Partitioning of (13)C to panicles and roots was higher under ozone treatment than in the control. Respiratory losses of fixed (13)C from plants tended to decrease under treatment with ozone. The increase in photoassimilate partitioning in panicles can be considered to be an acclimation response of rice plants to complete reproductive stage under the restricted biomass production caused by ozone.

Journal Article↗
PubMed1995

Characterization of Na+ transport across the cell membranes of the ascending thin limb of Henle's loop.

In the ascending thin limb of Henle's loop (ATL), intracellular Na+ is extruded by Na+/K+ ATPase in the basolateral membrane. To further characterize Na+ transport across the cell membranes of the ATL, the intracellular sodium concentration ([Na+]i) was monitored using a sodium-sensitive fluorescent probe, SBFI, in the in vitro microperfused hamster ATL. Basal [Na+]i was 19.0 +/- 1.2 mM (N = 24). Removal and replacement of luminal Na+ did not change [Na+]i in the presence of Na+ in the bathing fluid. In contrast, luminal Na+ removal reduced [Na+]i from 11.6 +/- 0.9 to 6.3 +/- 0.8 mM in the absence of peritubular Na+ (P < 0.0005, N = 21). Replacement of luminal Na+ increased [Na+]i to 12.6 +/- 0.9 mM. In the absence of Na+ in the bath, the addition of 1 microM benzamil, 0.1 mM 5-(N,N-dimethyl)-amiloride (DMA), 0.1 mM furosemide, or 0.1 mM trichlormethiazide to the lumen did not change [Na+]i or the rate of change in [Na+]i/dt) after removal and replacement of luminal Na+. Decreases in luminal pH in a Hepes-buffered solution and luminal HCO3- did not affect [Na+]i. In the absence of peritubular Na+, DMA in the bathing fluid decreased [Na+]i from 11.4 +/- 1.3 to 6.4 +/- 1.2 mM (P < 0.01, N = 5) and completely inhibited the changes in [Na+]i after removal and replacement of luminal Na+. Removal of peritubular Na+ reduced [Na+]i from 18.8 +/- 1.2 to 11.3 +/- 0.7 mM (P < 0.0001, N = 23). Addition of DMA in the bathing fluid reduced [Na+]i and inhibited the changes in [Na+]i after removal and replacement of peritubular Na+.(ABSTRACT TRUNCATED AT 250 WORDS)

Amiloride↗
PubMed1995

Pectoralis major myocutaneous flaps in rats.

A new neurovascular, island, myocutaneous flap, including the pectoralis major, was created in a rat model. This model is useful for the observation of muscle degeneration and skin changes due to ischemia or denervation. Although this model requires a delay procedure, it allows the flap, that can be used as a free myocutaneous flap, to be raised reliably.

Animals↗
PubMed1995

Cytosolic Ca2+ dynamics in hamster ascending thin limb of Henle's loop.

Intracellular calcium plays an important role in the regulation of Cl- reabsorption in the ascending thin limb of Henle's loop (ATL). To elucidate the cytosolic Ca2+ dynamics in the ATL, intracellular Ca2+ concentration activity ([Ca2+]i) was measured in the in vitro microperfused hamster ATL using fura 2. Basal [Ca2+]i was 89.1 +/- 7.3 nM (n = 9 tubules). Removal of Ca2+ from the peritubular solution decreased [Ca2+]i from 89.1 +/- 7.3 to 64.1 +/- 7.1 nM in 2 min (n = 9, P < 0.05), whereas [Ca2+]i did not change after removal of Ca2+ from the luminal solution. Addition of 1 mM NaCN to the bath increased [Ca2+]i. This effect was completely abolished by the elimination of ambient Ca2+. Trifluoperazine and N-(6-aminohexyl)-5-chloro-1-naphthalenesulfonamide (W-7) in the bath reversibly increased [Ca2+]i, whereas addition of 1 mM ouabain to the bath decreased [Ca2+]i. Rates of changes in [Ca2+]i after removal and replacement of basolateral Ca2+ were not affected by removal of Na+, K+, or Cl- from the bath, whereas nicardipine decreased these parameters. Increasing bath K+ from 5 to 100 mM decreased [Ca2+]i from 69.3 +/- 5.8 to 50.8 +/- 5.0 nM in 1 min (n = 6, P < 0.05). Subsequent reduction of K+ from 100 to 5 mM increased [Ca2+]i to 174.0 +/- 30.8 nM in 1 min, followed by a gradual decrease in [Ca2+]i to a steady-state level of 74.2 +/- 8.0 nM in 2 min. Changes in basolateral K+ concentration did not affect [Ca2+]i in the absence of ambient Ca2+.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Role of calcium in insulin-stimulated NaC1 transport in medullary thick ascending limb.

It has been reported that insulin stimulates directly NaCl transport in the rabbit medullary thick ascending limb (MTAL) [O. Ito, Y. Kondo, N. Takahashi, K. Kudo, Y. Imai, K. Omata, and K. Abe. Am. J. Physiol. 267 (Renal Fluid Electrolyte Physiol. 36): F265-F270, 1994]. In the present investigation, we evaluated the role of Ca2+ in insulin-stimulated NaCl transport in rabbit MTAL by in vitro microperfusion methods. In control experiments, insulin increases transepithelial voltage (Vte) and net lumen-to-bath Cl-flux (JCl). The effects of insulin on Vte and JCl in a Ca2+ -free solution containing ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N' -tetraacetic acid did not differ from those in a Ca2+ -containing control solution. Direct measurements of cytosolic free Ca2+ ([Ca2+]i) with fura 2 fluorescence showed that insulin caused no detectable change in [Ca2+]i in MTAL cells. Chelation of intracellular Ca2+ with the acetoxymethyl ester of 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid inhibited the actions of insulin in Vte and JCl without affecting basal values. We examined further whether calmodulin is also involved in insulin-stimulated NaCl transport in MTAL using two dissimilar inhibitors of calmodulin, trifluoperazine (TFP) and N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide (W-7). TFP and W-7 inhibited the action of insulin in a dose-dependent manner, with maximal inhibition of both agents of > 90%. The half-maximal inhibition by TFP and W-7 was approximately 50 and 100 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1995

Vasopressin stimulates Cl- transport in ascending thin limb of Henle's loop in hamster.

The effect of arginine vasopressin (AVP) on NaCl transport was investigated in the isolated microperfused hamster ascending thin limb of Henle's loop by measuring transepithelial voltage (Vt) and transmural 22Na+ and 36Cl- fluxes. In the presence of a transmural NaCl concentration gradient (100 mM higher in the lumen), Vt was 8.4 +/- 0.4 mV. Addition of 1 nM AVP to the basolateral solution increased Vt to 9.6 +/- 0.4 mV, which corresponds to an increase in the Cl- to Na+ permselectivity ratio (PCl/PNa) from 2.8 +/- 0.2 to 3.4 +/- 0.2. AVP at physiological concentrations increased Vt in a dose-dependent manner with an ED50 of 5 pM. AVP increased the Cl- efflux coefficient from 99.6 +/- 6.3 to 131.4 +/- 10.6 x 10(-7) cm2/s without affecting the Na+ efflux coefficient. 5-Nitro-2-(3-phenyl-propylamino)-benzoate (0.2 mM), a Cl- channel inhibitor, in the perfusate decreased the basal Cl- efflux coefficient and inhibited the AVP-induced increase in this parameter. The AVP-induced increase in Vt was not affected by [d(CH2)5(1),O-Me-Tyr2,Arg8] vasopressin, a V1 receptor antagonist, but was abolished by [d(CH2)5,D-Ile2,Ile4,Arg8] vasopressin, a V2 receptor antagonist. The selective V2 agonist dDAVP in 1 nM also increased Vt from 8.6 +/- 0.7 to 9.5 +/- 0.6 mV. Dibutyryl cAMP and forskolin both increased Vt, whereas H89, an inhibitor of cAMP-dependent protein kinase, abolished the AVP-induced increase in Vt. These results demonstrate that AVP stimulates Cl- transport in the ascending thin limb of Henle's loop by activating Cl- channels via a signal transduction cascade comprising V2 receptors, adenylate cyclase, and cAMP-dependent protein kinase. The ascending thin limb of Henle's loop thus participates in the formation of concentrated urine as one of the target renal tubular segments of AVP.

Adenylyl Cyclases↗
PubMed1995

Serum levels of soluble interleukin-2 receptor in chronic hepatitis C treated with interferon-alpha.

BACKGROUND: Serum levels of soluble interleukin-2 receptor (sIL-2R) seem to serve as a marker for the activation of T lymphocytes. The aim of this study was to evaluate the clinical significance of such levels in patients with chronic hepatitis C (CHC) treated with interferon. METHODS: We measured serum levels of sIL-2R in 37 patients with CHC before and after treatment with recombinant interferon-alpha. Serum receptor levels were then compared with the response of the hepatitis C virus (HCV)-RNA level in serum after interferon. RESULTS: Receptor levels were significantly higher in the patients with chronic persistent hepatitis and chronic active hepatitis than in normal controls (p < 0.01). There was a weak correlation between serum sIL-2R and alanine aminotransferase (ALAT) levels (r = 0.14, p = 0.010). Patients were then classified into three groups on the basis of the effect of interferon treatment on HCV-RNA levels in serum: sustained response (SR; n = 21), non-sustained response (NSR; n = 14), and nonresponse (NR; n = 2). Before and during interferon treatment the serum sIL-2R level remained increased in the SR group and in the combined groups with NSR or NR. However, after interferon was withdrawn, the serum sIL-2R decreased in the SR group but remained significantly increased in the combined response group (p < 0.01-0.05). CONCLUSION: This finding seems to reflect the disappearance of HCV-RNA from the serum of the patients with an SR, and monitoring of sIL-2R levels may therefore be of value as an adjunct to the measurement of serum ALAT and HCV-RNA in evaluating the response to the interferon therapy for CHC.

Adult↗
PubMed1995

Concomitant immunity against tumor development is enhanced by the oral administration of a kampo medicine, Hochu-ekki-to (TJ-41: Bu-Zhong-Yi-Qi-Tang).

The oral administration of a kampo herbal medicine, Hochu-ekki-to (TJ-41: Bu-Zhong-Yi-Qi-Tang) using a water-supplying bottle resulted in a slight but significant inhibition of Meth A growth. The oral administration of TJ-41 with gastric gavage significantly enhanced the specific antitumor activity against Meth A at rechallenge on day 9. In a tumor-neutralizing assay, the tumor draining LN cells of the TJ-41 administered mice showed an antitumor activity against Meth A. In a cytolytic assay, the anti-Meth A specific cytolytic T lymphocyte activity was not detected in the spleen cells of the Meth A bearing and TJ-41 administered mice. The oral administration of TJ-41 enhanced the natural killer (NK) activity of the spleen cells in naive mice but could not improve the decreased NK activity of spleen cells from the tumor bearing mice. In a cytostatic assay, the peritoneal exudate cells from the Meth A bearing and TJ-41 administered mice showed a significantly higher amount of cytostatic activity against Meth A than that from either Meth A bearing or TJ-41 administered mice. These results indicate that the oral administration of TJ-41 into the tumor bearing mice may thus be able to enhance concomitant antitumor immunity through the augmentation of the cytostatic activity.

Adjuvants, Immunologic↗
PubMed1995

[Electrolyte metabolism in renal tubules].

Obese, diabetic and hypertensive populations have an increased prevalence of hyperinsulinemia and insulin resistance with respect to glucose metabolism. Insulin is thought to contribute to hypertension by sodium retention in the kidney. Here we describe the direct effect of insulin on renal tubular transport. The ascending thin limb of Henle's loop (ATL) plays an important role in concentrating urine. However, it is still controversial whether Na+ reabsorption in this nephron segment is an active process or a passive one. Moreover hormonal regulation of Cl- transport in the ATL is completely unknown. Therefore we also describe the mechanism of Na+ transport and hormonal regulation of Cl- transport in the ATL.

Animals↗
PubMed1994

Functional difference between two isoforms of rat kidney prostaglandin receptor EP3 subtype.

We have cloned two isoforms of rat kidney prostaglandin E2 receptor EP3 subtype (rEP3A and rEP3B), which differ only in their cytosolic carboxyl-terminal tails (30 and 29 amino acids, respectively). The aim is to clarify the functional difference between two rEP3 receptor isoforms by examining formation of adenosine 3',5'-monophosphate (cAMP) and change in cytosolic free calcium ([Ca2+]i) in cultured cells transiently transfected with cloned rEP3A or rEP3B receptor cDNA. In immortalized renal distal tubule cells (TKC2), vasopressin (VP) stimulated cAMP formation, and the cAMP formation was significantly attenuated by a non-peptide VP receptor antagonist, OPC-31260. The VP-induced increase in cAMP formation was also attenuated by over-expression of rEP3A receptor but not that of rEP3B receptor. On the other hand, in COS-7 cells transfected with rEP3B receptor cDNA, PGE2 induced an increase in [Ca2+]i, but no increase in [Ca2+]i was observed in the cells transfected with rEP3A cDNA. In conclusion, rEP3A receptor is suggested to antagonize VP (V2) receptor by inhibiting cAMP formation, whereas rEP3B receptor is linked with Ca2+ messenger system.

Animals↗
PubMed1994

Generation of tumor-specific cytotoxic T lymphocytes in vivo by combined treatment with inactivated tumor cells and recombinant interleukin-2.

In order to search for a new therapy that would maximize the effect of interleukin-2 (IL-2) in evoking antitumor immunity in vivo, the therapeutic effect of a combination of mitomycin-C(MMC)-treated tumor cells and recombinant IL-2 was examined for its induction of antitumor activity against established melanoma metastasis. In C57BL/6 mice intravenously (i.v.) injected with B16 melanoma cells on day 0, the combined treatment with an intraperitoneal (i.p.) injection of MMC-treated melanoma cells on day 6 and 2500 U rIL-2 (twice daily) on days 7 and 8 markedly reduced the number of pulmonary metastases. This antitumor activity was more effective than that in untreated controls and mice that were injected with MMC-treated melanoma cells alone or rIL-2 alone. When the i.p. injection of MMC-treated tumor cells was replaced by other syngeneic tumor cells, antitumor activity against metastatic melanoma was not induced. The antitumor activity induced by this treatment increased in parallel with an increase in the dose of rIL-2 injected. In contrast, an i.p. injection of soluble tumor-specific antigens alone could induce only a marginal level of antitumor activity, and this activity was not augmented by subsequent i.p. injections of rIL-2. In vivo treatment with anti-CD8 monoclonal antibody (mAb), but not with anti-CD4 mAb or anti-asialo-GM1 antibody, abrogated the antitumor activity induced by this combined therapy. This suggests that the antitumor effect was dependent on CD8+ T cells. Lung-infiltrating lymphocytes from mice that had been i.v. injected with melanoma cells 11 days before and were treated with this combined therapy, showed melanoma-specific cytolytic activity. This combined therapy also showed significant antitumor activity against subcutaneously inoculated melanoma cells. These results demonstrate that the combined therapy of an i.p. injection of MMC-treated tumor cells and subsequent and consecutive i.p. administration of rIL-2 increases antitumor activity against established metastatic melanoma by generating tumor-specific CD8+ CTL in vivo.

Animals↗
PubMed1994

Th1 type CD4+ T cells may be a potent effector against poorly immunogenic syngeneic tumors.

We examined the possibility that Th1 type CD4+ T cells may be an effector against three kinds of syngeneic tumors such as highly immunogenic B16 melanoma (B16) and two poorly immunogenic lines of MCA fibrosarcoma (MCA) and 3LL carcinoma (3LL). In a proliferation assay, the Th1 type CD4+ T cell clone (MH2) recognized the purified protein derivatives (PPD) derived from Mycobacterium tuberculosis. In a tumor-neutralizing assay, MH2 showed anti-tumor activity against both B16 and MCA. In a model of pulmonary metastasis, MH2 also showed anti-tumor activity against both B16 and 3LL. In an assay of cytolysis, MH2 showed a moderate level of tumor necrosis factor-dependent cytolytic activity only against MCA. In a cytostasis assay, MH2 showed a high level of interferon gamma-dependent cytostatic activity against the three tumors in the presence of macrophages. The anti-tumor activity of MH2 against B16 and 3LL was suggested to be, at least in part, attributable to the augmented natural killer activity. Taken together, these findings suggest that we may potentially be able to utilize Th1 type CD4+ T cells as an effector for immunotherapy against poorly immunogenic tumors.

Animals↗