Immunotherapy with irradiated autologous leukemic cells in patients with B-CLL in early stages

Abstract

Abstract. In this study 10 7 peripheral blood mononuclear cells including on average 78.56% CD19 + /CD5 + lymphocytes were irradiated, and then administered intradermally as an anti-cancer vaccine to seventeen patients with B-cell chronic lymphocytic leukemia (B-CLL) at early stages (twelve injections, four at a weekly interval followed by eight vaccines given every two weeks). In eight out of seventeen patients, in the first two injections, irradiated leukemic cells were mixed with Bacillus Calmette-Guerin (BCG) to improve the efficacy of therapy by additional induction of innate immunity. A hematological improvement (as defined by a >25% reduction of leukocyte count) to autologous leukemic cell vaccines was observed in 5/17 patients, stabilisation of disease in 5/17 patients and in 7/17 patients there was no response to immunotherapy. In seven patients significant increase of the lymphocyte doubling time was noted (p=0.02). There was no impact of BCG for immune responses or clinical outcome of vaccinated patients, but there was a significant increase of the absolute counts of CD3 + as well as of CD3 + /CD4 + and CD3 + /CD8 + T cells during the vaccination period. We observed a significant improvement of the phagocytic function of autologous dendritic cells generated from peripheral blood monocytes obtained from patients with B-CLL after the end of immunotherapy (p=0.006). An association between the clinical outcome and the percentage of leukemic cells positive for expression of ZAP-70 and CD38 was noted. In conclusion, our results demonstrated the feasibility and safety of autologous irradiated leukemic cell immunotherapy in patients with B-CLL. As we noted immunological, and to some extent, clinical responses, this approach merits further investigation, including the use of adjuvants other than BCG. IntroductionB-cell chronic lymphocytic leukemia (B-CLL) is the most common leukemia in western countries. The clinical course of B-CLL can be quite variable. Many patients survive many years with a good quality of life (QOL) without receiving any therapy, whereas others succumb rapidly despite aggressive treatment (1). It was established that treatment of early stage disease carries no benefit over a management of watching and waiting for progression (2). However, ~50% of patients with early stage disease develop a more advanced disease and will die from B-CLL and its complications. Therefore, it might be appropriate to reconsider the strategy of early therapy in B-CLL patients particularly those with high-risk prognostic factors. Most novel treatments, including purine analogues, monoclonal antibodies and combination immunochemotherapy, have significant risks for infectious complications (3,4), which must be carefully weighted against the risks emerging from the underlying disease. Thus, cellular immunotherapies might constitute an advantageous therapeutical option, inhibiting disease progression and delaying the start of chemotherapy in early stage patients with relatively small tumor mass. The purpose of cancer...

SCID mice model in vivo evaluation of autologous and allogeneic dendritic cells activity on B-cell chronic lymphocytic leukemia.

“…The observed unresponsiveness of patients own T lymphocytes to autologous dendritic cells may be partly explained by B-CLL patient's DCs defective phagocytosis recently recorded [3]. We observed, that the vaccination of patients with the irradiated leukemia cells improve of DCs phagocytotic activity.…”

“…Since it is a slow growing malignancy, the time allows for an immunotherapy attempts against the tumor cells to be generated by vaccination [2,3]. It is easy to obtain tumor cells for vaccine production, as the leukemia cells circulate in large amounts in peripheral blood.…”

RHAMM-target peptides inhibit invasion of breast cancer cells

“…Therefore, we need a development the novel anticancer drugs with higher specificity, low toxicity, selective targeting cancer cells and without side effects. RHAMM is ideal molecular target for anti-cancer therapeutic agents, because it is hyper expressed in tumour tissues, such as breast cancer (60,61,71), leukemia (72), colon cancer (73), oral squamous cell carcinoma (74), aggressive fibromatosis (75), endometrial carcinoma (76,77) as well as multiple myeloma (58).…”

Cancer immunotherapy in mice and humans: personal observations*

“…The procedure did not induce significant adverse effects, except for some small redness of the skin at the injection site, and sometimes a temperature rise of 1 o C on the following day. Long-term observation of patients over a number of years did not disclose any adverse problems related to the vaccination [36,37].…”

“…Leukocyte (WBC) and lymphocyte trend curves of a patient with B-CLL treated with irradiated leukemia cell vaccines from the time of initial diagnosis during immunotherapy to twelve months after the end of vaccination (patient from hematological improvement group)[37]. Arrows -time of vaccine injections.…”