Journal of Immunology and Clinical Research

Prospects in Adoptive Cell Transfer Therapy for Cancer

Review Article | Open Access

  • 1. Institute for Tumor Immunology, Ludong University College of Life Sciences, 186 Hongqi Middle Road, Yantai, Shandong 264025, China
  • 2. Department of Pathology, Microbiology and Immunology, School of Medicine, University of South Carolina, 6439 Garners Ferry Road, Columbia, SC 29209, USA
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Corresponding Authors
Juhua Zhou, Institute for Tumor Immunology, Ludong University School of Life Sciences, 186 Hongqi Middle Road, Yantai, Shandong 264025, PR China

Cancer treatment still is a challenge task for both basic scientists and clinicians. Conventional treatments for cancer such as surgery, radiation and chemotherapy seem inadequate. Recent developments in immunotherapy make it a more promising method for cancer treatment. Clinical trials have demonstrated that adoptive cell transfer therapy using anti-tumor tumor-infiltrating lymphocytes is very effective in the treatment of patients with metastatic melanoma. Genetically-engineered T lymphocytes with anti-tumor activities may also be used effectively in adoptive cell transfer therapy for cancer. It is, therefore, desirable to establish a bank of anti-tumor tumor-infiltrating lymphocytes and/or genetically-engineered anti-tumor T lymphocytes, which are active against all known tumor antigens. This program may provide an effective adoptive cell transfer therapy for cancer patients in the future as long as specific tumor antigens are identified.


•    Adoptive cell transfer therapy (ACT)
•    Lymphokine-activated killer (LAK) cells
•    Cytokine-induced killer (CIK) cells
•    Tumor-infiltrating lymphocytes (TIL)
•    Genetically-engineered T lymphocytes


Li Y, Huang Q, Zhong Y, Wang A, Sun J, et al. (2013) Prospects in Adoptive Cell Transfer Therapy for Cancer. J Immunol Clin Res 1: 1008.


It has been documented that immunosurveillance plays an important role in cancer development in both human and animals [1,2]. Cancer immunosurveillance is the function of immune system in recognizing and reacting against aberrant cancer cells in the body. Thus, the interactions between cancer cells and immune cells play a pivotal role in cancer development. In cancer patients, however, tumors grow, suggesting that antitumor immune responses are either not sufficiently vigorous to eliminate cancer cells or the anti-tumor immunity is suppressed.

Recent clinical trials have demonstrated that adoptive cell transfer therapy (ACT) with anti-tumor lymphocytes can cause cancer regression in approximately 70% of patients with metastatic melanoma [3,4]. Therefore, in vitro manipulation of anti-tumor immunity may be used in the effective treatment of cancer patients. In this review, the development and prospects of ACT for cancer are discussed. Cancer immunotherapy has been noted as one of six Areas to Watch in 2013 [5], and it is expected that ACT with anti-tumor lymphocytes will be extensively used in cancer treatment in the near future.


LAK cells are the activated peripheral blood mononuclear cells (PBMC) from cancer patient and normal donors after in vitro stimulation by interleukin-2 (IL-2) for 4-6 days [6]. They are derived from natural killer (NK) and T cells in PBMC. LAK cells have anti-tumor activity in vitro against various cancer cells. In 1984, it was demonstrated that LAK cells in combination with IL-2 were very effective in eradicating tumors in mice with established pulmonary sarcoma metastases [7]. In 1985, Rosenberg et al. used LAK cells for ACT in clinical trials for patients with metastatic cancer [8]. After ACT with LAK cells, the reduction of tumor burdens was achieved in approximately 50% of the 25 treated patients and one patient had a complete tumor regression [8]. However, the response in cancer patients was sustained only for a short period of time [9]. The antitumor activity of LAK cells is maintained by IL-2, and thus highdose of IL-2 (2.8×105 -3.32×106 U/kg) is required for ACT of LAK cells in cancer treatment. Moreover, IL-2 induced serious side effects such as capillary leak syndrome (CLS) or vascular leakage syndrome (VLS) [10,11]. Further studies showed that LAK cells did not prove effective in the treatment of metastatic melanoma and renal cancer patients [12]. In addition, clinical trials discovered that IL-2 administration alone could induce tumor regression in 20% of patients with metastatic melanoma and renal cancer [12]. Therefore, ACT with LAK cells is currently not used in cancer treatment.


CIK cells are also activated PBMC after in vitro stimulation by multiple factors including interferon-γ (IFN-γ), IL-1α, IL-2 and anti-CD3 antibody for 7-14 days [13]. They are mainly CD3+ CD56+ cells, i. e. NK cell-like T cells. Similar to LAK cells, CIK cells can kill varieties of tumor cells in vitro and in vivo mouse models [13,14]. Nowadays, autologous CIK cells have been extensively used in treatment of cancer patients in China although the effectiveness and mechanisms of ACT with CIK cells are still uncertain [15-18].

Due to the lack of tumor antigen specificities of CIK cells and strong capability of antigen presentation of dendritic cells (DC), DC-CIK cells were recently developed for ACT for cancer. Usually, DCs from peripheral blood samples were pulsed by tumor antigens, tumor lysate or antigen-loaded viral vectors and then co-cultured with CIK cells to grow DC-CIK cells. Compared with CIK cells alone, DC-CIK cells have increased proliferation ability, cytokine secretion and anti-tumor activity [19,20]. Therefore, it is believed that DC-CIK cells are more effective than CIK cells alone in ACT for cancer patients. A clinical trial showed that ACT with tumor lysate-pulsed DC-CIK cells could significantly increase overall survival rates than no treatment control in renal cancer carcinoma patients; however, there was no difference between ACT with DC-CIK cells and IFN-α administration (P > 0.05) [21]. Thus, the efficacy of ACT with DC-CIK cells in cancer treatment remains to be determined.


(TILS) It has been documented that TILs could be easily generated from metastatic melanoma patients [22,23]. After expansion, TILs have anti-tumor activity against autologous tumor cells and other cancer cells [22,23]. Clinical trials have demonstrated that ACT with anti-tumor TILs can induce tumor regression in 49- 72% of the treated patients with metastatic melanoma [3,24], suggesting that ACT with anti-tumor TILs is an effective method in cancer treatment.

Our studies discovered that the persistence of multiple anti-tumor T cell clones was responsible for tumor regression in metastatic melanoma patients after ACT of anti-tumor TILs [25,26]. We subsequently demonstrated that the telomere length of transferred lymphocytes was associated with T cell persistence and clinical response in patients with metastatic melanoma after ACT [27,28], suggesting that less-proliferated young TILs would be more effective for ACT [29,30]. Thus, telomere length may be used as a marker to select TILs for ACT in order to improve the efficacy of ACT with anti-tumor TILs for cancer patients.


As mentioned above, ACT of anti-tumor TILs is an effective method for patients with metastatic melanoma. Anti-tumor tumor-infiltrated lymphocytes, however, may not be generated from all cancer patients. Thus, genetically-engineered T lymphocytes with anti-tumor activity are pursued for ACT for cancer [31]. Usually, viral vectors carrying genes coding T-cell receptor genes specific to tumor antigens or chimeric antigen receptors (CARs) are genetically introduced into PBMC or tumorinfiltrating lymphocytes [30,32,33]. Such genetically-engineered T lymphocytes have high avidity and tumor reactivity [34], which may be used for ACT in cancer treatment. For instance, genetically-engineered T lymphocytes are highly reactive to MART-1 melanoma tumor antigen [35]. In addition, infusion of CD19-specific CAR-transduced mouse T cells alone could induce long-term B cell eradication in mouse model of B cell acute lymphoblastic leukemia (B-ALL) [36] and primary human pre-Bcell acute lymphoblastic leukemia [33].

A clinical trial indicated that genetically-engineered T lymphocytes reactive to MART-1 for ACT might be effective in tumor regression in metastatic melanoma patients [4]. Genetically-engineered T lymphocytes reactive to NY-ESO-1 also successfully induced tumor regression in both melanoma patients and nonmelanoma synovial cell sarcoma patients [37]. Furthermore, infusion of genetically-engineered T cells with CD19-specific CARs caused rapid tumor regression in patients with relapsed/refractory B-ALL [38] and advanced chronic lymphocytic leukemia (CLL) [39]. Thus, genetically-engineered T lymphocytes with anti-tumor reactivities may be used in ACT for cancer patients, from whom anti-tumor tumor-infiltrating lymphocytes cannot be generated for therapy.


Thus far, there is no evidence available to confirm that ACT of CIK cells and DC-CIK cells is effective in cancer treatment. However, it may be effective when ACT of CIK cells and DCCIK cells is used together with conventional cancer treatment methods. For instance, ACT with CIK cells in combination with chemotherapy had potential benefits including longer progression-free survival and overall survival in patients with advanced gastric cancer and non-small-cell lung cancer as compared with chemotherapy alone [40,41]. The combination of high-dose chemotherapy with ACT of DC-CIK cells showed clinical benefits such as improved progression-free survival and overall survival in metastatic breast cancer patients [38]. ACT of DC-CIK cells in combination with chemotherapy also could significantly increase the 1- and 2-year overall survival rates in patients with advanced non-small-cell lung cancer [42]. Therefore, ACT of CIK cells and DC-CIK cells in combination with conventional cancer treatments such as chemotherapy may be used as effective treatment modalities for cancer patients.

ACT of anti-tumor TILs has been shown to be effective in the treatment of patients with metastatic melanoma [3]. TILs can also be generated from patients with breast cancer [43], renal cancer [44], pancreatic cancer [45] and lung cancer [23]. These lymphocytes have anti-tumor activity against autologous tumor cells and other cancer cells [23,43,45]. Therefore, ACT using antitumor TILs is a promising effective treatment for patients with breast cancer, renal cancer, etc.

Genetically-engineered T lymphocytes with anti-tumor activity against MART-1 seem to be effective in ACT for metastatic melanoma patients [4]. It is possible that genetically-engineered T lymphocytes with anti-tumor activities against other tumor antigens may be effectively used in ACT for other forms of cancer [37]. It is desirable to establish a bank of genetically-engineered T lymphocytes with anti-tumor reactivities against all known tumor antigens. It will facilitate future applications of ACT as an effective treatment for cancer patients as long as specific tumor antigens are identified. For a similar reason, it is worthwhile to establish a bank of anti-tumor TILs from different cancer patients for future ACT in cancer treatment.

In vitro generation of anti-tumor TILs is critical for successful ACT in cancer treatment. The flexibility in manipulations of T cells in vitro would overcome tumor-induced T-cell anergy in vivo to generate optimal anti-tumor immunity. Anti-tumor TILs may used in the identification of antigens involved in tumor regression mediated by transferred anti-tumor lymphocytes [25,46]. Understanding of antigen specificities in anti-tumor TILs for ACT will have great implications in exploring the mechanism of tumor regression induced by transferred T cells and improving the efficacy of ACT in cancer treatment [25,47]. Furthermore, identification of antigen specificities in anti-tumor TILs would facilitate the generation of genetically-engineered T lymphocytes with anti-tumor activities against specific tumor antigens for ACT.

CTLA-4 (cytotoxic T-lymphocyte antigen-4) interacting with its ligands (B7.1 and B7.2) down-regulates the immune system and thus antibodies that block the interaction between CTLA-4 and its ligands can increase immune responses. Recent studies have shown that monoclonal antibody therapy using anti-CTLA-4, PD-1 (programmed death-1) and CD137 (4-1BB) monoclonal antibodies can enhance immune responses, including anti-tumor immunity [48]. Clinical trials in metastatic melanoma patients demonstrated that antibody therapy with anti-CTLA-4 antibodies (lpilimumab and tremelimumab) could induce melanoma regression and/or improve overall patient survival although serious side effects were found in 10-25% of patients [49-51]. NY-ESO-1 and gp100 vaccination in combination with anti-CTLA-4 antibody therapy increased the vaccine-primed antigen-specific T-cell response in metastatic melanoma patients [51,52]. Therefore, ACT in combination with antibody therapy may provide a promising strategy for improved ACT efficacy in cancer treatment.


This work was supported by “Taishan Scholar” Special Fund (No. 109, 2012) from Shandong Government, China.


1. Doll R, Kinlen L. Immunosurveillance and cancer: epidemiological evidence. Br Med J. 1970; 4: 420-422.

2. Clark CE, Beatty GL, Vonderheide RH. Immunosurveillance of pancreatic adenocarcinoma: insights from genetically engineered mouse models of cancer. Cancer Lett. 2009; 279: 1-7.

3. Dudley ME, Yang JC, Sherry R, Hughes MS, Royal R, Kammula U, et al. Adoptive cell therapy for patients with metastatic melanoma: evaluation of intensive myeloablative chemoradiation preparative regimens. J Clin Oncol. 2008; 26: 5233-5239.

4. Morgan RA, Dudley ME, Wunderlich JR, Hughes MS, Yang JC, Sherry RM, et al. Cancer regression in patients after transfer of genetically engineered lymphocytes. Science. 2006; 314: 126-129.

5. No authors listed] Breakthrough of the year. Areas to watch. Science. 2012; 338: 1528-1529.

6. Grimm EA, Mazumder A, Zhang HZ, Rosenberg SA. Lymphokineactivated killer cell phenomenon. Lysis of natural killer-resistant fresh solid tumor cells by interleukin 2-activated autologous human peripheral blood lymphocytes. J Exp Med. 1982; 155: 1823-1841.

7. Mulé JJ, Shu S, Schwarz SL, Rosenberg SA. Adoptive immunotherapy of established pulmonary metastases with LAK cells and recombinant interleukin-2. Science. 1984; 225: 1487-1489.

8. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Ettinghausen SE, et al. Observations on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2 to patients with metastatic cancer. N Engl J Med. 1985; 313: 1485-1492.

9. Rosenberg SA, Lotze MT, Muul LM, Chang AE, Avis FP, Leitman S, et al. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987; 316: 889-897.

10. Rosenberg SA, Lotze MT, Muul LM, Leitman S, Chang AE, Vetto JT, et al. A new approach to the therapy of cancer based on the systemic administration of autologous lymphokine-activated killer cells and recombinant interleukin-2. Surgery. 1986; 100: 262-272.

11. Den Otter W, Jacobs JJ, Battermann JJ, Hordijk GJ, Krastev Z, Moiseeva EV, et al. Local therapy of cancer with free IL-2. Cancer Immunol Immunother. 2008; 57: 931-950.

12. Kammula US, Marincola FM. Cancer immunotherapy: is there real progress at last? BioDrugs. 1999; 11: 249-260.

13. Schmidt-Wolf IG, Negrin RS, Kiem HP, Blume KG, Weissman IL. Use of a SCID mouse/human lymphoma model to evaluate cytokine-induced killer cells with potent antitumor cell activity. J Exp Med. 1991; 174: 139-149.

14. Wang FS, Liu MX, Zhang B, Shi M, Lei ZY, Sun WB, et al. Antitumor activities of human autologous cytokine-induced killer (CIK) cells against hepatocellular carcinoma cells in vitro and in vivo. World J Gastroenterol. 2002; 8: 464-468.

15. Jiang JT, Shen YP, Wu CP, Zhu YB, Wei WX, Chen LJ, et al. Increasing the frequency of CIK cells adoptive immunotherapy may decrease risk of death in gastric cancer patients. World J Gastroenterol. 2010; 16: 6155-6162.

16. Luo H, Zhou X. [Researche advances on CIK cells and their clinical use in lung cancer]. Zhongguo Fei Ai Za Zhi. 2011; 14: 954-959.

17. Wang Y, Bo J, Dai HR, Lu XC, Lv HY, Yang B, et al. CIK cells from recurrent or refractory AML patients can be efficiently expanded in vitro and used for reduction of leukemic blasts in vivo. Exp Hematol. 2013; 41: 241-252.

18. Li XD, Xu B, Wu J, Ji M, Xu BH, Jiang JT, et al. Review of Chinese clinical trials on CIK cell treatment for malignancies. Clin Transl Oncol. 2012; 14: 102-108.

19. Zhang S, Wang EZ, Bai CX, Xu YH. [The proliferation profile in vitro and anti-tumor effects of dendritic cells co-culturing with CIK cells]. Shi Yan Sheng Wu Xue Bao. 2003; 36: 375-380.

20. Wei XC, Zhai XH, Han XR, Yang DD, Zhao WL. Biological activity of DCCIK cells and its effect against leukemia cells in vitro. Zhongguo Shi Yan Xue Ye Xue Za Zhi. 2008; 16: 1150-1153.

21. Zhan HL, Gao X, Pu XY, Li W, Li ZJ, Zhou XF, et al. A randomized controlled trial of postoperative tumor lysate-pulsed dendritic cells and cytokine-induced killer cells immunotherapy in patients with localized and locally advanced renal cell carcinoma. Chin Med J (Engl). 2012; 125: 3771-3777.

22. Dudley ME, Wunderlich JR, Shelton TE, Even J, Rosenberg SA. Generation of tumor-infiltrating lymphocyte cultures for use in adoptive transfer therapy for melanoma patients. J Immunother. 2003; 26: 332-342.

23. Goff SL, Smith FO, Klapper JA, Sherry R, Wunderlich JR, Steinberg SM, et al. Tumor infiltrating lymphocyte therapy for metastatic melanoma: analysis of tumors resected for TIL. J Immunother. 2010; 33: 840-847.

24. Rosenberg SA, Yang JC, Sherry RM, Kammula US, Hughes MS, Phan GQ, et al. Durable complete responses in heavily pretreated patients with metastatic melanoma using T-cell transfer immunotherapy. Clin Cancer Res. 2011; 17: 4550-4557.

25. Zhou J, Dudley ME, Rosenberg SA, Robbins PF. Persistence of multiple tumor-specific T-cell clones is associated with complete tumor regression in a melanoma patient receiving adoptive cell transfer therapy. J Immunother. 2005; 28: 53-62.

26. Robbins PF, Dudley ME, Wunderlich J, El-Gamil M, Li YF, Zhou J et al. Cutting edge: persistence of transferred lymphocyte clonotypes correlates with cancer regression in patients receiving cell transfer therapy. J Immunol. 2004; 173: 7125-7130.

27. Zhou J, Shen X, Huang J, Hodes RJ, Rosenberg SA, Robbins PF. Telomere length of transferred lymphocytes correlates with in vivo persistence and tumor regression in melanoma patients receiving cell transfer therapy. J Immunol. 2005; 175: 7046-7052.

28. Shen X, Zhou J, Hathcock KS, Robbins P, Powell DJ Jr, Rosenberg SA, et al. Persistence of tumor infiltrating lymphocytes in adoptive immunotherapy correlates with telomere length. J Immunother. 2007; 30: 123-129.

29. Tran KQ, Zhou J, Durflinger KH, Langhan MM, Shelton TE, Wunderlich JR, et al. Minimally cultured tumor-infiltrating lymphocytes display optimal characteristics for adoptive cell therapy. J Immunother. 2008; 31: 742-751.

30. Stroncek DF, Berger C, Cheever MA, Childs RW, Dudley ME, Flynn P, et al. New directions in cellular therapy of cancer: a summary of the summit on cellular therapy for cancer. J Transl Med. 2012; 10: 48.

31. Park TS, Rosenberg SA, Morgan RA. Treating cancer with genetically engineered T cells. Trends Biotechnol. 2011; 29: 550-557.

32. Davies JK, Singh H, Huls H, Yuk D, Lee DA, Kebriaei P, et al. Combining CD19 redirection and alloanergization to generate tumor-specific human T cells for allogeneic cell therapy of B-cell malignancies. Cancer Res. 2010; 70: 3915-3924.

33. Milone MC, Fish JD, Carpenito C, Carroll RG, Binder GK, Teachey D, et al. Chimeric receptors containing CD137 signal transduction domains mediate enhanced survival of T cells and increased antileukemic efficacy in vivo. Mol Ther. 2009; 17: 1453-1464.

34. Johnson LA, Heemskerk B, Powell DJ Jr, Cohen CJ, Morgan RA, Dudley ME, et al. Gene transfer of tumor-reactive TCR confers both high avidity and tumor reactivity to nonreactive peripheral blood mononuclear cells and tumor-infiltrating lymphocytes. J Immunol. 2006; 177: 6548-6559.

35. Hughes MS, Yu YY, Dudley ME, Zheng Z, Robbins PF, Li Y, et al. Transfer of a TCR gene derived from a patient with a marked antitumor response conveys highly active T-cell effector functions. Hum Gene Ther. 2005; 16: 457-472.

36. Davila ML, Kloss CC, Gunset G, Sadelain M. CD19 CAR-targeted T cells induce long-term remission and B Cell Aplasia in an immunocompetent mouse model of B cell acute lymphoblastic leukemia. PLoS One. 2013; 8: e61338.

37. Robbins PF, Morgan RA, Feldman SA, Yang JC, Sherry RM, Dudley ME, et al. Tumor regression in patients with metastatic synovial cell sarcoma and melanoma using genetically engineered lymphocytes reactive with NY-ESO-1. J Clin Oncol. 2011; 29: 917-924.

38. Brentjens RJ, Davila ML, Riviere I, Park J, Wang X, Cowell LG, et al. CD19-targeted T cells rapidly induce molecular remissions in adults with chemotherapy-refractory acute lymphoblastic leukemia. Sci Transl Med. 2013; 5: 177ra38.

39. Kalos M, Levine BL, Porter DL, Katz S, Grupp SA, Bagg A, et al. T cells with chimeric antigen receptors have potent antitumor effects and can establish memory in patients with advanced leukemia. Sci Transl Med. 2011; 3: 95ra73.

40. Jiang J, Xu N, Wu C, Deng H, Lu M, Li M, et al. Treatment of advanced gastric cancer by chemotherapy combined with autologous cytokineinduced killer cells. Anticancer Res. 2006; 26: 2237-2242.

41. Wu C, Jiang J, Shi L, Xu N. Prospective study of chemotherapy in combination with cytokine-induced killer cells in patients suffering from advanced non-small cell lung cancer. Anticancer Res. 2008; 28: 3997-4002.

42. Yang L, Ren B, Li H, Yu J, Cao S, Hao X, et al. Enhanced antitumor effects of DC-activated CIKs to chemotherapy treatment in a single cohort of advanced non-small-cell lung cancer patients. Cancer Immunol Immunother. 2013; 62: 65-73.

43. Zhou J, Zhong Y. Breast cancer immunotherapy. Cell Mol Immunol. 2004; 1: 247-255.

44. Liotta F, Gacci M, Frosali F, Querci V, Vittori G, Lapini A, et al. Frequency of regulatory T cells in peripheral blood and in tumour-infiltrating lymphocytes correlates with poor prognosis in renal cell carcinoma. BJU Int. 2011; 107: 1500-1506.

45. Frankel TL, Burns W, Riley J, Morgan RA, Davis JL, Hanada K, et al. Identification and characterization of a tumor infiltrating CD56(+)/ CD16 (-) NK cell subset with specificity for pancreatic and prostate cancer cell lines. Cancer Immunol Immunother. 2010; 59: 1757-1769.

46. Robbins PF, Lu YC, El-Gamil M, Li YF, Gross C, Gartner J, et al. Mining exomic sequencing data to identify mutated antigens recognized by adoptively transferred tumor-reactive T cells. Nat Med. 2013; 19: 747- 752.

47. Lu YC, Yao X, Li YF, El-Gamil M, Dudley ME, Yang JC, et al. Mutated PPP1R3B is recognized by T cells used to treat a melanoma patient who experienced a durable complete tumor regression. J Immunol. 2013; 190: 6034-6042.

48. Simeone E, Ascierto PA. Immunomodulating antibodies in the treatment of metastatic melanoma: the experience with anti-CTLA-4, anti-CD137, and anti-PD1. J Immunotoxicol. 2012; 9: 241-247.

49. Lipson EJ, Drake CG. Ipilimumab: an anti-CTLA-4 antibody for metastatic melanoma. Clin Cancer Res. 2011; 17: 6958-6962.

50. Ribas A. Clinical development of the anti-CTLA-4 antibody tremelimumab. Semin Oncol. 2010; 37: 450-4.

51. Yuan J, Gnjatic S, Li H, Powel S, Gallardo HF, Ritter E, et al. CTLA-4 blockade enhances polyfunctional NY-ESO-1 specific T cell responses in metastatic melanoma patients with clinical benefit. Proc Natl Acad Sci U S A. 2008; 105: 20410-20415.

52. Yuan J, Ginsberg B, Page D, Li Y, Rasalan T, Gallardo HF, et al. CTLA4 blockade increases antigen-specific CD8(+) T cells in prevaccinated patients with melanoma: three cases. Cancer Immunol Immunother. 2011; 60: 1137-1146.

Received : 13 Jul 2013
Accepted : 08 Aug 2013
Published : 14 Aug 2013
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Annals of Gerontology and Geriatric Research
ISSN : 2378-9409
Launched : 2014
Journal of Sleep Medicine and Disorders
ISSN : 2379-0822
Launched : 2014
JSM Burns and Trauma
ISSN : 2475-9406
Launched : 2016
Chemical Engineering and Process Techniques
ISSN : 2333-6633
Launched : 2013
Annals of Clinical Cytology and Pathology
ISSN : 2475-9430
Launched : 2014
JSM Allergy and Asthma
ISSN : 2573-1254
Launched : 2016
Journal of Neurological Disorders and Stroke
ISSN : 2334-2307
Launched : 2013
Annals of Sports Medicine and Research
ISSN : 2379-0571
Launched : 2014
JSM Sexual Medicine
ISSN : 2578-3718
Launched : 2016
Annals of Vascular Medicine and Research
ISSN : 2378-9344
Launched : 2014
JSM Biotechnology and Biomedical Engineering
ISSN : 2333-7117
Launched : 2013
Journal of Hematology and Transfusion
ISSN : 2333-6684
Launched : 2013
JSM Environmental Science and Ecology
ISSN : 2333-7141
Launched : 2013
Journal of Cardiology and Clinical Research
ISSN : 2333-6676
Launched : 2013
JSM Nanotechnology and Nanomedicine
ISSN : 2334-1815
Launched : 2013
Journal of Ear, Nose and Throat Disorders
ISSN : 2475-9473
Launched : 2016
JSM Ophthalmology
ISSN : 2333-6447
Launched : 2013
Journal of Pharmacology and Clinical Toxicology
ISSN : 2333-7079
Launched : 2013
Annals of Psychiatry and Mental Health
ISSN : 2374-0124
Launched : 2013
Medical Journal of Obstetrics and Gynecology
ISSN : 2333-6439
Launched : 2013
Annals of Pediatrics and Child Health
ISSN : 2373-9312
Launched : 2013
JSM Clinical Pharmaceutics
ISSN : 2379-9498
Launched : 2014
JSM Foot and Ankle
ISSN : 2475-9112
Launched : 2016
JSM Alzheimer's Disease and Related Dementia
ISSN : 2378-9565
Launched : 2014
Journal of Addiction Medicine and Therapy
ISSN : 2333-665X
Launched : 2013
Journal of Veterinary Medicine and Research
ISSN : 2378-931X
Launched : 2013
Annals of Public Health and Research
ISSN : 2378-9328
Launched : 2014
Annals of Orthopedics and Rheumatology
ISSN : 2373-9290
Launched : 2013
Journal of Clinical Nephrology and Research
ISSN : 2379-0652
Launched : 2014
Annals of Community Medicine and Practice
ISSN : 2475-9465
Launched : 2014
Annals of Biometrics and Biostatistics
ISSN : 2374-0116
Launched : 2013
JSM Clinical Case Reports
ISSN : 2373-9819
Launched : 2013
Journal of Cancer Biology and Research
ISSN : 2373-9436
Launched : 2013
Journal of Surgery and Transplantation Science
ISSN : 2379-0911
Launched : 2013
Journal of Dermatology and Clinical Research
ISSN : 2373-9371
Launched : 2013
JSM Gastroenterology and Hepatology
ISSN : 2373-9487
Launched : 2013
Annals of Nursing and Practice
ISSN : 2379-9501
Launched : 2014
JSM Dentistry
ISSN : 2333-7133
Launched : 2013
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